Table of Contents Author Guidelines Submit a Manuscript
Neural Plasticity
Volume 2007, Article ID 78171, 12 pages
http://dx.doi.org/10.1155/2007/78171
Review Article

Neurobiology of Memory and Anxiety: From Genes to Behavior

Laboratory of Clinical Science, Division of Intramural Research Program (DIRP), National Institute of Mental Health (NIMH), Bethesda, MD 20892-1264, USA

Received 15 May 2006; Revised 15 November 2006; Accepted 16 November 2006

Academic Editor: Georges Chapouthier

Copyright © 2007 Allan V. Kalueff. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. Y. Clement and G. Chapouthier, “Biological bases of anxiety,” Neuroscience and Biobehavioral Reviews, vol. 22, no. 5, pp. 623–633, 1998. View at Publisher · View at Google Scholar
  2. D. J. Nutt, “Neurobiological mechanisms in generalized anxiety disorder,” Journal of Clinical Psychiatry, vol. 62, 11, pp. 22–27, 2001. View at Google Scholar
  3. D. J. Nutt, “Overview of diagnosis and drug treatments of anxiety disorders,” CNS Spectrums, vol. 10, no. 1, pp. 49–56, 2005. View at Google Scholar
  4. D. J. Nutt and A. L. Malizia, “New insights into the role of the GABAA-benzodiazepine receptor in psychiatric disorder,” British Journal of Psychiatry, vol. 179, pp. 390–396, 2001. View at Publisher · View at Google Scholar
  5. D. J. Nutt, J. C. Ballenger, D. Sheehan, and H.-U. Wittchen, “Generalized anxiety disorder: comorbidity, comparative biology and treatment,” International Journal of Neuropsychopharmacology, vol. 5, no. 4, pp. 315–325, 2002. View at Publisher · View at Google Scholar
  6. K. R. Bailey, N. R. Rustay, and J. N. Crawley, “Behavioral phenotyping of transgenic and knockout mice: practical concerns and potential pitfalls,” ILAR Journal, vol. 47, no. 2, pp. 124–131, 2006. View at Google Scholar
  7. J. N. Crawley, “Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions, motor abilities, and specific behavioral tests,” Brain Research, vol. 835, no. 1, pp. 18–26, 1999. View at Publisher · View at Google Scholar
  8. MGI, “Mouse Genome Informatics,” 2006, http://www.informatics.jax.org/. View at Google Scholar
  9. MPD, “Mouse Phenome Database,” 2006, http://phenome.jax.org/pub-cgi/phenome/mpdcgi. View at Google Scholar
  10. N. Singewald, P. Salchner, and T. Sharp, “Induction of c-Fos expression in specific areas of the fear circuitry in rat forebrain by anxiogenic drugs,” Biological Psychiatry, vol. 53, no. 4, pp. 275–283, 2003. View at Publisher · View at Google Scholar
  11. A. Dagnino-Subiabre, J. A. Orellana, C. Carmona-Fontaine et al., “Chronic stress decreases the expression of sympathetic markers in the pineal gland and increases plasma melatonin concentration in rats,” Journal of Neurochemistry, vol. 97, no. 5, pp. 1279–1287, 2006. View at Publisher · View at Google Scholar
  12. A. V. Kalueff and D. J. Nutt, “Role of GABA in memory and anxiety,” Depression and Anxiety, vol. 4, no. 3, pp. 100–110, 1996. View at Publisher · View at Google Scholar
  13. P. M. Wall and C. Messier, “Concurrent modulation of anxiety and memory,” Behavioural Brain Research, vol. 109, no. 2, pp. 229–241, 2000. View at Publisher · View at Google Scholar
  14. R. M. Yerkes and J. D. Dodson, “The relation of strength of stimulus to rapidity of habit-formation,” Journal of Comparative Neurology and Psychology, vol. 18, no. 5, pp. 459–482, 1908. View at Publisher · View at Google Scholar
  15. M. Barad, “Fear extinction in rodents: basic insight to clinical promise,” Current Opinion in Neurobiology, vol. 15, no. 6, pp. 710–715, 2005. View at Publisher · View at Google Scholar
  16. A. Beuzen and C. Belzung, “Link between emotional memory and anxiety states: a study by principal component analysis,” Physiology and Behavior, vol. 58, no. 1, pp. 111–118, 1995. View at Publisher · View at Google Scholar
  17. G. Chapouthier and P. Venault, “GABAA receptor complex and memory processes,” Current Topics in Medicinal Chemistry, vol. 2, no. 8, pp. 841–851, 2002. View at Publisher · View at Google Scholar
  18. R. Gerlai, “Memory enhancement: the progress and our fears,” Genes, Brain and Behavior, vol. 2, no. 4, pp. 187–190, 2003. View at Publisher · View at Google Scholar
  19. M. B. Parent, M. K. Habib, and G. B. Baker, “Time-dependent changes in brain monoamine oxidase activity and in brain levels of monoamines and amino acids following acute administration of the antidepressant/antipanic drug phenelzine,” Biochemical Pharmacology, vol. 59, no. 10, pp. 1253–1263, 2000. View at Publisher · View at Google Scholar
  20. G. J. Quirk and D. R. Gehlert, “Inhibition of the amygdala: key to pathological states?” Annals of the New York Academy of Sciences, vol. 985, pp. 263–272, 2003. View at Google Scholar
  21. I. Izquierdo and J. H. Medina, “GABAA receptor modulation of memory: the role of endogenous benzodiazepines,” Trends in Pharmacological Sciences, vol. 12, no. 7, pp. 260–265, 1991. View at Publisher · View at Google Scholar
  22. I. Izquierdo and J. H. Medina, “Correlation between the pharmacology of long-term potentiation and the pharmacology of memory,” Neurobiology of Learning and Memory, vol. 63, no. 1, pp. 19–32, 1995. View at Publisher · View at Google Scholar
  23. D. M. Bannerman, J. N. P. Rawlins, S. B. McHugh et al., “Regional dissociations within the hippocampus—memory and anxiety,” Neuroscience and Biobehavioral Reviews, vol. 28, no. 3, pp. 273–283, 2004. View at Publisher · View at Google Scholar
  24. E. J. M. Bierman, H. C. Comijs, C. Jonker, and A. T. F. Beekman, “Effects of anxiety versus depression on cognition in later life,” American Journal of Geriatric Psychiatry, vol. 13, no. 8, pp. 686–693, 2005. View at Publisher · View at Google Scholar
  25. W. El Hage, S. Peronny, G. Griebel, and C. Belzung, “Impaired memory following predatory stress in mice is improved by fluoxetine,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 28, no. 1, pp. 123–128, 2004. View at Publisher · View at Google Scholar
  26. W. El Hage, G. Griebel, and C. Belzung, “Long-term impaired memory following predatory stress in mice,” Physiology and Behavior, vol. 87, no. 1, pp. 45–50, 2006. View at Publisher · View at Google Scholar
  27. R. L. Ribeiro, R. Andreatini, C. Wolfman, H. Viola, J. H. Medina, and C. Da Cunha, “The ‘anxiety state’ and its relation with rat models of memory and habituation,” Neurobiology of Learning and Memory, vol. 72, no. 2, pp. 78–94, 1999. View at Publisher · View at Google Scholar
  28. M. M. Savić, D. I. Obradović, N. D. Ugrešić, and D. R. Bokonjić, “Memory effects of benzodiazepines: memory stages and types versus binding-site subtypes,” Neural Plasticity, vol. 12, no. 4, pp. 289–298, 2005. View at Google Scholar
  29. M. M. Savić, D. I. Obradović, N. D. Ugrešić, J. M. Cook, P. V. V. S. Sarma, and D. R. Bokonjić, “Bidirectional effects of benzodiazepine binding site ligands on active avoidance acquisition and retention: differential antagonism by flumazenil and β-CCt,” Psychopharmacology, vol. 180, no. 3, pp. 455–465, 2005. View at Publisher · View at Google Scholar
  30. M. M. Savić, D. I. Obradović, N. D. Ugrešić, J. M. Cook, W. Yin, and D. R. Bokonjić, “Bidirectional effects of benzodiazepine binding site ligands in the passive avoidance task: differential antagonism by flumazenil and β-CCt,” Behavioural Brain Research, vol. 158, no. 2, pp. 293–300, 2005. View at Publisher · View at Google Scholar
  31. J. A. Gingrich and R. Hen, “Dissecting the role of the serotonin system in neuropsychiatric disorders using knockout mice,” Psychopharmacology, vol. 155, no. 1, pp. 1–10, 2001. View at Publisher · View at Google Scholar
  32. L. M. Monteggia, M. Barrot, C. M. Powell et al., “Essential role of brain-derived neurotrophic factor in adult hippocampal function,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 29, pp. 10827–10832, 2004. View at Publisher · View at Google Scholar
  33. M. Rios, G. Fan, C. Fekete et al., “Conditional deletion of brain-derived neurotrophic factor in the postnatal brain leads to obesity and hyperactivity,” Molecular Endocrinology, vol. 15, no. 10, pp. 1748–1757, 2001. View at Publisher · View at Google Scholar
  34. J. M. Wehner and S. A. Balogh, “Genetic studies of learning and memory in mouse models,” in Behavioral Genetics in the Postgenomic Era, R. Plomin, J. DeFries, I. Craig, and P. McGuffin, Eds., pp. 103–121, APA, Washington, DC, USA, 2002. View at Google Scholar
  35. S. A. Ross, J. Y. F. Wong, J. J. Clifford et al., “Phenotypic characterization of an α4 neuronal nicotinic acetylcholine receptor subunit knock-out mouse,” Journal of Neuroscience, vol. 20, no. 17, pp. 6431–6441, 2000. View at Google Scholar
  36. R. Paylor, M. Nguyen, J. N. Crawley, J. Patrick, A. Beaudet, and A. Orr-Urtreger, “α7 nicotinic receptor subunits are not necessary for hippocampal- dependent learning or sensorimotor gating: a behavioral characterization of Acra7-deficient mice,” Learning and Memory, vol. 5, no. 4-5, pp. 302–316, 1998. View at Google Scholar
  37. M. R. Picciotto, M. Zoli, C. Léna et al., “Abnormal avoidance learning in mice lacking functional high-affinity nicotine receptor in the brain,” Nature, vol. 374, no. 6517, pp. 65–67, 1995. View at Publisher · View at Google Scholar
  38. M.-C. Buhot, G. Malleret, and L. Segu, “Serotonin receptors and cognitive behaviour—an update,” IDrugs, vol. 2, no. 5, pp. 426–437, 1999. View at Google Scholar
  39. M.-C. Buhot, M. Wolff, M. Savova, G. Malleret, R. Hen, and L. Segu, “Protective effect of 5-HT1B receptor gene deletion on the age-related decline in spatial learning abilities in mice,” Behavioural Brain Research, vol. 142, no. 1-2, pp. 135–142, 2003. View at Publisher · View at Google Scholar
  40. A. Dirks, T. Pattij, J. A. Bouwknecht et al., “5-HT1B receptor knockout, but not 5-HT1A receptor knockout mice, show reduced startle reactivity and footshock-induced sensitization, as measured with the acoustic startle response,” Behavioural Brain Research, vol. 118, no. 2, pp. 169–178, 2001. View at Publisher · View at Google Scholar
  41. C. López-Rubalcava, R. Hen, and S. L. Cruz, “Anxiolytic-like actions of toluene in the burying behavior and plus-maze tests: differences in sensitivity between 5-HT(1B) knockout and wild-type mice,” Behavioural Brain Research, vol. 115, no. 1, pp. 85–94, 2000. View at Publisher · View at Google Scholar
  42. M. Wolff, M. Savova, G. Malleret, R. Hen, L. Segu, and M.-C. Buhot, “Serotonin 1B knockout mice exhibit a task-dependent selective learning facilitation,” Neuroscience Letters, vol. 338, no. 1, pp. 1–4, 2003. View at Publisher · View at Google Scholar
  43. C. L. Parks, P. S. Robinson, E. Sibille, T. Shenk, and M. Toth, “Increased anxiety of mice lacking the serotonin1A receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 18, pp. 10734–10739, 1998. View at Publisher · View at Google Scholar
  44. Z. Sarnyai, E. L. Sibille, C. Pavlides, R. J. Fenster, B. S. McEwen, and M. Tóth, “Impaired hippocampal-dependent learning and functional abnormalities in the hippocampus in mice lacking serotonin1A receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 26, pp. 14731–14736, 2000. View at Publisher · View at Google Scholar
  45. E. Sibille, C. Pavlides, D. Benke, and M. Toth, “Genetic inactivation of the serotonin(1A) receptor in mice results in downregulation of major GABAA receptor α subunits, reduction of GABAA receptor binding, and benzodiazepine-resistant anxiety,” Journal of Neuroscience, vol. 20, no. 8, pp. 2758–2765, 2000. View at Google Scholar
  46. R. Grailhe, C. Waeber, S. C. Dulawa et al., “Increased exploratory activity and altered response to LSD in mice lacking the 5-HT(5A) receptor,” Neuron, vol. 22, no. 3, pp. 581–591, 1999. View at Publisher · View at Google Scholar
  47. A. Holmes, D. L. Murphy, and J. N. Crawley, “Abnormal behavioral phenotypes of serotonin transporter knockout mice: parallels with human anxiety and depression,” Biological Psychiatry, vol. 54, no. 10, pp. 953–959, 2003. View at Publisher · View at Google Scholar
  48. F. Crestani, R. Keist, J.-M. Fritschy et al., “Trace fear conditioning involves hippocampal α5 GABAA receptors,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 13, pp. 8980–8985, 2002. View at Publisher · View at Google Scholar
  49. F. Crestani, M. Lorez, K. Baer et al., “Decreased GABAA-receptor clustering results in enhanced anxiety and a bias for threat cues,” Nature Neuroscience, vol. 2, no. 9, pp. 833–839, 1999. View at Publisher · View at Google Scholar
  50. A. Rizk, J. Curley, J. Robertson, and J. Raber, “Anxiety and cognition in histamine H3 receptor / mice,” European Journal of Neuroscience, vol. 19, no. 7, pp. 1992–1996, 2004. View at Publisher · View at Google Scholar
  51. H. Toyota, C. Dugovic, M. Koehl et al., “Behavioral characterization of mice lacking histamine H3 receptors,” Molecular Pharmacology, vol. 62, no. 2, pp. 389–397, 2002. View at Publisher · View at Google Scholar
  52. B. K. Yee, E. Balic, P. Singer et al., “Disruption of glycine transporter 1 restricted to forebrain neurons is associated with a procognitive and antipsychotic phenotypic profile,” Journal of Neuroscience, vol. 26, no. 12, pp. 3169–3181, 2006. View at Publisher · View at Google Scholar
  53. D. R. Shimshek, T. Bus, J. Kim et al., “Enhanced odor discrimination and impaired olfactory memory by spatially controlled switch of AMPA receptors,” PLoS Biology, vol. 3, no. 11, p. e354, 2005. View at Publisher · View at Google Scholar
  54. M. Masugi, M. Yokoi, R. Shigemoto et al., “Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear response and conditioned taste aversion,” Journal of Neuroscience, vol. 19, no. 3, pp. 955–963, 1999. View at Google Scholar
  55. D. M. Bannerman, R. M. J. Deacon, S. Brady et al., “A comparison of GluR-A-deficient and wild-type mice on a test battery assessing sensorimotor, affective, and cognitive behaviors,” Behavioral Neuroscience, vol. 118, no. 3, pp. 643–647, 2004. View at Publisher · View at Google Scholar
  56. J. Grimsby, M. Toth, K. Chen et al., “Increased stress response and beta-phenylethylamine in MAOB-deficient mice,” Nature Genetics, vol. 17, no. 2, pp. 206–210, 1997. View at Publisher · View at Google Scholar
  57. K. Chen, D. P. Holschneider, W. Wu, I. Rebrini, and J. C. Shih, “A spontaneous point mutation produces monoamine oxidase A/B knock-out mice with greatly elevated monoamines and anxiety-like behavior,” Journal of Biological Chemistry, vol. 279, no. 38, pp. 39645–39652, 2004. View at Publisher · View at Google Scholar
  58. A. Contarino, F. Dellu, G. F. Koob et al., “Reduced anxiety-like and cognitive performance in mice lacking the corticotropin-releasing factor receptor 1,” Brain Research, vol. 835, no. 1, pp. 1–9, 1999. View at Publisher · View at Google Scholar
  59. A. Guadaño-Ferraz, R. Benavides-Piccione, C. Venero et al., “Lack of thyroid hormone receptor α1 is associated with selective alterations in behavior and hippocampal circuits,” Molecular Psychiatry, vol. 8, no. 1, pp. 30–38, 2003. View at Publisher · View at Google Scholar
  60. C. Venero, A. Guadaño-Ferraz, A. I. Herrero et al., “Anxiety, memory impairment, and locomotor dysfunction caused by a mutant thyroid hormone receptor α1 can be ameliorated by T3 treatment,” Genes and Development, vol. 19, no. 18, pp. 2152–2163, 2005. View at Publisher · View at Google Scholar
  61. B. Greco and M. Carli, “Reduced attention and increased impulsivity in mice lacking NPY Y2 receptors: relation to anxiolytic-like phenotype,” Behavioural Brain Research, vol. 169, no. 2, pp. 325–334, 2006. View at Publisher · View at Google Scholar
  62. H. Nishiyama, T. Knöpfel, S. Endo, and S. Itohara, “Glial protein S100B modulates long-term neuronal synaptic plasticity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 6, pp. 4037–4042, 2002. View at Publisher · View at Google Scholar
  63. A. Abeliovich, R. Paylor, C. Chen, J. J. Kim, J. M. Wehner, and S. Tonegawa, “PKCγ mutant mice exhibit mild deficits in spatial and contextual learning,” Cell, vol. 75, no. 7, pp. 1263–1271, 1993. View at Publisher · View at Google Scholar
  64. B. J. Bowers, A. C. Collins, T. Tritto, and J. M. Wehner, “Mice lacking PKCγ exhibit decreased anxiety,” Behavior Genetics, vol. 30, no. 2, pp. 111–121, 2000. View at Publisher · View at Google Scholar
  65. C. J. M. Bontekoe, K. L. McIlwain, I. M. Nieuwenhuizen et al., “Knockout mouse model for Fxr2: a model for mental retardation,” Human Molecular Genetics, vol. 11, no. 5, pp. 487–498, 2002. View at Publisher · View at Google Scholar
  66. U. Müller, N. Cristina, Z.-W. Li et al., “Behavioral and anatomical deficits in mice homozygous for a modified β-amyloid precursor protein gene,” Cell, vol. 79, no. 5, pp. 755–765, 1994. View at Google Scholar
  67. C. Otto, M. Martin, D. P. Wolfer, H.-P. Lipp, R. Maldonado, and G. Schütz, “Altered emotional behavior in PACAP-type-I-receptor-deficient mice,” Molecular Brain Research, vol. 92, no. 1-2, pp. 78–84, 2001. View at Publisher · View at Google Scholar
  68. C. Otto, Y. Kovalchuk, D. P. Wolfer et al., “Impairment of mossy fiber long-term potentiation and associative learning in pituitary adenylate cyclase activating polypeptide type I receptor-deficient mice,” Journal of Neuroscience, vol. 21, no. 15, pp. 5520–5527, 2001. View at Google Scholar
  69. S. Yang, M. Farias, D. Kapfhamer et al., “Biochemical, molecular and behavioral phenotypes of Rab3A mutations in the mouse,” to appear in Genes, Brain and Behavior.
  70. P. D'Adamo, D. R. Wolfer, C. Kopp, I. Tobler, D. Toniolo, and H.-P. Lipp, “Mice deficient for the synaptic vesicle protein Rab3a show impaired spatial reversal learning and increased explorative activity but none of the behavioral changes shown by mice deficient for the Rab3a regulator Gdi1,” European Journal of Neuroscience, vol. 19, no. 7, pp. 1895–1905, 2004. View at Publisher · View at Google Scholar
  71. S. L. Rauch, B. A. Van Der Kolk, R. E. Fisler et al., “A symptom provocation study of posttraumatic stress disorder using positron emission tomography and script-driven imagery,” Archives of General Psychiatry, vol. 53, no. 5, pp. 380–387, 1996. View at Google Scholar
  72. E. A. Phelps, K. J. O'Connor, J. C. Gatenby, J. C. Gore, C. Grillon, and M. Davis, “Activation of the left amygdala to a cognitive representation of fear,” Nature Neuroscience, vol. 4, no. 4, pp. 437–441, 2001. View at Publisher · View at Google Scholar
  73. J. S. Morris, K. J. Friston, C. Büchel et al., “A neuromodulatory role for the human amygdala in processing emotional facial expressions,” Brain, vol. 121, no. 1, pp. 47–57, 1998. View at Publisher · View at Google Scholar
  74. W. D. S. Killgore and D. A. Yurgelun-Todd, “Activation of the amygdala and anterior cingulate during nonconscious processing of sad versus happy faces,” NeuroImage, vol. 21, no. 4, pp. 1215–1223, 2004. View at Publisher · View at Google Scholar
  75. W. D. S. Killgore and D. A. Yurgelun-Todd, “Social anxiety predicts amygdala activation in adolescents viewing fearful faces,” NeuroReport, vol. 16, no. 15, pp. 1671–1675, 2005. View at Publisher · View at Google Scholar
  76. C. H. Bueno, H. Zangrossi Jr., R. L. Nogueira, V. P. Soares, and M. B. Viana, “Panicolytic-like effect induced by the stimulation of GABAA and GABAB receptors in the dorsal periaqueductal grey of rats,” European Journal of Pharmacology, vol. 516, no. 3, pp. 239–246, 2005. View at Publisher · View at Google Scholar
  77. C. H. Bueno, H. Zangrossi Jr., and M. B. Viana, “The inactivation of the basolateral nucleus of the rat amygdala has an anxiolytic effect in the elevated T-maze and light/dark transition tests,” Brazilian Journal of Medical and Biological Research, vol. 38, no. 11, pp. 1697–1701, 2005. View at Publisher · View at Google Scholar
  78. C. W. Spanis, M. M. Bianchin, I. Izquierdo, and J. L. McGaugh, “Excitotoxic basolateral amygdala lesions potentiate the memory impairment effect of muscimol injected into the medial septal area,” Brain Research, vol. 816, no. 2, pp. 329–336, 1999. View at Publisher · View at Google Scholar
  79. B. Mei, C. Li, S. Dong, C. H. Jiang, H. Wang, and Y. Hu, “Distinct gene expression profiles in hippocampus and amygdala after fear conditioning,” Brain Research Bulletin, vol. 67, no. 1-2, pp. 1–12, 2005. View at Publisher · View at Google Scholar
  80. D. M. Yilmazer-Hanke, T. Roskoden, K. Zilles, and H. Schwegler, “Anxiety-related behavior and densities of glutamate, GABAA, acetylcholine and serotonin receptors in the amygdala of seven inbred mouse strains,” Behavioural Brain Research, vol. 145, no. 1-2, pp. 145–159, 2003. View at Publisher · View at Google Scholar
  81. C. Caldji, J. Diorio, H. Anismam, and M. J. Meaney, “Maternal behavior regulates benzodiazepine/GABAA receptor subunit expression in brain regions associated with fear in BALB/c and C57BL/6 mice,” Neuropsychopharmacology, vol. 29, no. 7, pp. 1344–1352, 2004. View at Publisher · View at Google Scholar
  82. C. Da Cunha, M. L. De Stein, C. Wolfman, R. Koya, I. Izquierdo, and J. H. Medina, “Effect of various training procedures on performance in an elevated plus-maze: possible relation with brain regional levels of benzodiazepine-like molecules,” Pharmacology Biochemistry and Behavior, vol. 43, no. 3, pp. 677–681, 1992. View at Publisher · View at Google Scholar
  83. M. T. Rogan, K. S. Leon, D. L. Perez, and E. R. Kandel, “Distinct neural signatures for safety and danger in the amygdala and striatum of the mouse,” Neuron, vol. 46, no. 2, pp. 309–320, 2005. View at Publisher · View at Google Scholar
  84. O. Stork, F.-Y. Ji, and K. Obata, “Reduction of extracellular GABA in the mouse amygdala during and following confrontation with a conditioned fear stimulus,” Neuroscience Letters, vol. 327, no. 2, pp. 138–142, 2002. View at Publisher · View at Google Scholar
  85. G. Wik, M. Fredrikson, K. Ericson, L. Eriksson, S. Stone-Elander, and T. Greitz, “A functional cerebral response to frightening visual stimulation,” Psychiatry Research - Neuroimaging, vol. 50, no. 1, pp. 15–24, 1993. View at Publisher · View at Google Scholar
  86. J. D. Bremner, M. Narayan, L. H. Staib, S. M. Southwick, T. McGlashan, and D. S. Charney, “Neural correlates of memories of childhood sexual abuse in women with and without posttraumatic stress disorder,” American Journal of Psychiatry, vol. 156, no. 11, pp. 1787–1795, 1999. View at Google Scholar
  87. L. Zhang, D. R. Rubinow, W. Ma et al., “GABA receptor subunit mRNA expression in brain of conflict, yoked control and control rats,” Molecular Brain Research, vol. 58, no. 1-2, pp. 16–26, 1998. View at Publisher · View at Google Scholar
  88. R. Kalisch, M. Schubert, W. Jacob et al., “Anxiety and hippocampus volume in the rat,” Neuropsychopharmacology, vol. 31, no. 5, pp. 925–932, 2006. View at Publisher · View at Google Scholar
  89. B. Zimmerberg, S. A. Brunelli, A. J. Fluty, and C. A. Frye, “Differences in affective behaviors and hippocampal allopregnanolone levels in adult rats of lines selectively bred for infantile vocalizations,” Behavioural Brain Research, vol. 159, no. 2, pp. 301–311, 2005. View at Publisher · View at Google Scholar
  90. K. Zilles, J. Wu, W. E. Crusio, and H. Schwegler, “Water maze and radial maze learning and the density of binding sites of glutamate, GABA, and serotonin receptors in the hippocampus of inbred mouse strains,” Hippocampus, vol. 10, no. 3, pp. 213–225, 2000. View at Publisher · View at Google Scholar
  91. J. A. Hobin, J. Ji, and S. Maren, “Ventral hippocampal muscimol disrupts context-specific fear memory retrieval after extinction in rats,” Hippocampus, vol. 16, no. 2, pp. 174–182, 2006. View at Publisher · View at Google Scholar
  92. D. Jerusalinsky, E. Kornisiuk, and I. Izquierdo, “Cholinergic neurotransmission and synaptic plasticity concerning memory processing,” Neurochemical Research, vol. 22, no. 4, pp. 507–515, 1997. View at Publisher · View at Google Scholar
  93. Y. Abe, A. Aoyagi, T. Hara et al., “Pharmacological characterization of RS-1259, an orally active dual inhibitor of acetylcholinesterase and serotonin transporter, in rodents: possible treatment of Alzheimer's disease,” Journal of Pharmacological Sciences, vol. 93, no. 1, pp. 95–105, 2003. View at Publisher · View at Google Scholar
  94. E. R. Korpi, G. Gründer, and H. Lüddens, “Drug interactions at GABAA receptors,” Progress in Neurobiology, vol. 67, no. 2, pp. 113–159, 2002. View at Publisher · View at Google Scholar
  95. E. R. Korpi and S. T. Sinkkonen, “GABAA receptor subtypes as targets for neuropsychiatric drug development,” Pharmacology and Therapeutics, vol. 109, no. 1-2, pp. 12–32, 2006. View at Publisher · View at Google Scholar
  96. T. W. Rosahl, “Validation of GABAA receptor subtypes as potential drug targets by using genetically modified mice,” Current Drug Targets. CNS and Neurological Disorders, vol. 2, no. 4, pp. 207–212, 2003. View at Publisher · View at Google Scholar
  97. S. Vicini and P. Ortinski, “Genetic manipulations of GABAA receptor in mice make inhibition exciting,” Pharmacology and Therapeutics, vol. 103, no. 2, pp. 109–120, 2004. View at Publisher · View at Google Scholar
  98. S. V. Argyropoulos and D. J. Nutt, “The use of benzodiazepines in anxiety and other disorders,” European Neuropsychopharmacology, vol. 9, 6, pp. S407–S412, 1999. View at Publisher · View at Google Scholar
  99. R. B. Lydiard, “The role of GABA in anxiety disorders,” Journal of Clinical Psychiatry, vol. 64, 3, pp. 21–27, 2003. View at Google Scholar
  100. U. Rudolph and H. Möhler, “GABA-based therapeutic approaches: GABAA receptor subtype functions,” Current Opinion in Pharmacology, vol. 6, no. 1, pp. 18–23, 2006. View at Publisher · View at Google Scholar
  101. J. J. Sandford, S. V. Argyropoulos, and D. J. Nutt, “The psychobiology of anxiolytic drugs - Part 1: basic neurobiology,” Pharmacology and Therapeutics, vol. 88, no. 3, pp. 197–212, 2000. View at Publisher · View at Google Scholar
  102. S. V. Argyropoulos, J. J. Sandford, and D. J. Nutt, “The psychobiology of anxiolytic drugs. Part 2: pharmacological treatments of anxiety,” Pharmacology and Therapeutics, vol. 88, no. 3, pp. 213–227, 2000. View at Publisher · View at Google Scholar
  103. R. O. Beleboni, R. O. G. Carolino, A. B. Pizzo et al., “Pharmacological and biochemical aspects of GABAergic neurotransmission: pathological and neuropsychobiological relationships,” Cellular and Molecular Neurobiology, vol. 24, no. 6, pp. 707–728, 2004. View at Publisher · View at Google Scholar
  104. F. De-Paris, J. V. Busnello, M. R. M. Vianna et al., “The anticonvulsant compound gabapentin possesses anxiolytic but not amnesic effects in rats,” Behavioural Pharmacology, vol. 11, no. 2, pp. 169–173, 2000. View at Google Scholar
  105. A. P. Lang and L. De Angelis, “Experimental anxiety and antiepileptics: the effects of valproate and vigabatrin in the mirrored chamber test,” Methods and Findings in Experimental and Clinical Pharmacology, vol. 25, no. 4, pp. 265–271, 2003. View at Publisher · View at Google Scholar
  106. C. B. Nemeroff, “The role of GABA in the pathophysiology and treatment of anxiety disorders,” Psychopharmacology Bulletin, vol. 37, no. 4, pp. 133–146, 2003. View at Google Scholar
  107. S. M. Stahl, “Anticonvulsants as anxiolytics, part 1: tiagabine and other anticonvulsants with actions on GABA,” The Journal of Clinical Psychiatry, vol. 65, no. 3, pp. 291–292, 2004. View at Google Scholar
  108. I. Akirav, H. Raizel, and M. Maroun, “Enhancement of conditioned fear extinction by infusion of the GABAA agonist muscimol into the rat prefrontal cortex and amygdala,” European Journal of Neuroscience, vol. 23, no. 3, pp. 758–764, 2006. View at Publisher · View at Google Scholar
  109. J. P. Chhatwal, K. M. Myers, K. J. Ressler, and M. Davis, “Regulation of gephyrin and GABAA receptor binding within the amygdala after fear acquisition and extinction,” Journal of Neuroscience, vol. 25, no. 2, pp. 502–506, 2005. View at Publisher · View at Google Scholar
  110. C. McCabe, D. Shaw, J. R. Atack et al., “Subtype-selective GABAergic drugs facilitate extinction of mouse operant behaviour,” Neuropharmacology, vol. 46, no. 2, pp. 171–178, 2004. View at Publisher · View at Google Scholar
  111. M. R. Zarrindast, A. Bakhsha, P. Rostami, and B. Shafaghi, “Effects of intrahippocampal injection of GABAergic drugs on memory retention of passive avoidance learning in rats,” Journal of Psychopharmacology, vol. 16, no. 4, pp. 313–319, 2002. View at Google Scholar
  112. M.-R. Zarrindast, M. Noorbakhshnia, F. Motamedi, A. Haeri-Rohani, and A. Rezayof, “Effect of the GABAergic system on memory formation and state-dependent learning induced by morphine in rats,” Pharmacology, vol. 76, no. 2, pp. 93–100, 2006. View at Publisher · View at Google Scholar
  113. G. Chapouthier and P. Venault, “GABAA receptor complex and memory processes,” Medicinal Chemistry Reviews, vol. 1, no. 1, pp. 91–99, 2004. View at Publisher · View at Google Scholar
  114. V. Birzniece, T. Bäckström, I.-M. Johansson et al., “Neuroactive steroid effects on cognitive functions with a focus on the serotonin and GABA systems,” Brain Research Reviews, vol. 51, no. 2, pp. 212–239, 2006. View at Publisher · View at Google Scholar
  115. S. Blum, A. E. Hebert, and P. K. Dash, “A role for the prefrontal cortex in recall of recent and remote memories,” NeuroReport, vol. 17, no. 3, pp. 341–344, 2006. View at Publisher · View at Google Scholar
  116. D. Chandra, E. R. Korpi, C. P. Miralles, A. L. de Blas, and G. E. Homanics, “GABAA receptor γ2 subunit knockdown mice have enhanced anxiety-like behavior but unaltered hypnotic response to benzodiazepines,” BMC Neuroscience, vol. 6, Article ID 30, 13 pages, 2005. View at Publisher · View at Google Scholar
  117. A. Marowsky, J.-M. Fritschy, and K. E. Vogt, “Functional mapping of GABAA receptor subtypes in the amygdala,” European Journal of Neuroscience, vol. 20, no. 5, pp. 1281–1289, 2004. View at Publisher · View at Google Scholar
  118. B. K. Yee, J. Hauser, V. V. Dolgov et al., “GABAA receptors containing the α5 subunit mediate the trace effect in aversive and appetitive conditioning and extinction of conditioned fear,” European Journal of Neuroscience, vol. 20, no. 7, pp. 1928–1936, 2004. View at Publisher · View at Google Scholar
  119. H. Wang, Y. Z. Zhu, P. T.-H. Wong et al., “cDNA microarray analysis of gene expression in anxious PVG and SD rats after cat-freezing test,” Experimental Brain Research, vol. 149, no. 4, pp. 413–421, 2003. View at Google Scholar
  120. J. M. Verkuyl, S. E. Hemby, and M. Jöels, “Chronic stress attenuates GABAergic inhibition and alters gene expression of parvocellular neurons in rat hypothalamus,” European Journal of Neuroscience, vol. 20, no. 6, pp. 1665–1673, 2004. View at Publisher · View at Google Scholar
  121. M. Kosel, U. Rudolph, P. Wielepp et al., “Diminished GABAA receptor-binding capacity and a DNA base substitution in a patient with treatment-resistant depression and anxiety,” Neuropsychopharmacology, vol. 29, no. 2, pp. 347–350, 2004. View at Publisher · View at Google Scholar
  122. S. Sen, S. Villafuerte, R. Nesse et al., “Serotonin transporter and GABAA alpha 6 receptor variants are associated with neuroticism,” Biological Psychiatry, vol. 55, no. 3, pp. 244–249, 2004. View at Publisher · View at Google Scholar
  123. J. Feusner, T. Ritchie, B. Lawford, R. M. Young, B. Kann, and E. P. Noble, “GABAA receptor β3 subunit gene and psychiatric morbidity in a post-traumatic stress disorder population,” Psychiatry Research, vol. 104, no. 2, pp. 109–117, 2001. View at Publisher · View at Google Scholar
  124. M. Uhart, M. E. McCaul, L. M. Oswald, L. Choi, and G. S. Wand, “GABRA6 gene polymorphism and an attenuated stress response,” Molecular Psychiatry, vol. 9, no. 11, pp. 998–1006, 2004. View at Publisher · View at Google Scholar
  125. S. Maren and G. J. Quirk, “Neuronal signalling of fear memory,” Nature Reviews Neuroscience, vol. 5, no. 11, pp. 844–852, 2004. View at Publisher · View at Google Scholar
  126. H.-C. Pape and O. Stork, “Genes and mechanisms in the amygdala involved in the formation of fear memory,” Annals of the New York Academy of Sciences, vol. 985, pp. 92–105, 2003. View at Google Scholar
  127. U. Schmitt and C. Hiemke, “Tiagabine, a γ-amino-butyric acid transporter inhibitor impairs spatial learning of rats in the Morris water-maze,” Behavioural Brain Research, vol. 133, no. 2, pp. 391–394, 2002. View at Publisher · View at Google Scholar
  128. J. R. Atack, “Anxioselective compounds acting at the GABAA receptor benzodiazepine binding site,” Current Drug Targets. CNS and Neurological Disorders, vol. 2, no. 4, pp. 213–232, 2003. View at Publisher · View at Google Scholar
  129. J. R. Atack, “The benzodiazepine binding site of GABAA receptors as a target for the development of novel anxiolytics,” Expert Opinion on Investigational Drugs, vol. 14, no. 5, pp. 601–618, 2005. View at Publisher · View at Google Scholar
  130. J. R. Atack, P. H. Hutson, N. Collinson et al., “Anxiogenic properties of an inverse agonist selective for α3 subunit-containing GABAA receptors,” British Journal of Pharmacology, vol. 144, no. 3, pp. 357–366, 2005. View at Publisher · View at Google Scholar
  131. J.-H. Hu, Y.-H. Ma, J. Jiang et al., “Cognitive impairment in mice over-expressing γ-aminobutyric acid transporter 1 (GAT1),” NeuroReport, vol. 15, no. 1, pp. 9–12, 2004. View at Publisher · View at Google Scholar
  132. H. Möhler, J.-M. Fritschy, F. Crestani, T. Hensch, and U. Rudolph, “Specific GABAA circuits in brain development and therapy,” Biochemical Pharmacology, vol. 68, no. 8, pp. 1685–1690, 2004. View at Publisher · View at Google Scholar
  133. T. J. Bushell, G. Sansig, R. Shigemoto et al., “An impairment of hippocampal synaptic plasticity in mice lacking mGlu7 receptors,” Neuropharmacology, vol. 35, no. 6, p. A6, 1996. View at Publisher · View at Google Scholar
  134. H. Garpenstrand, P. Annas, J. Ekblom, L. Oreland, and M. Fredrikson, “Human fear conditioning is related to dopaminergic and serotonergic biological markers,” Behavioral Neuroscience, vol. 115, no. 2, pp. 358–364, 2001. View at Publisher · View at Google Scholar
  135. M. A. Pezze and J. Feldon, “Mesolimbic dopaminergic pathways in fear conditioning,” Progress in Neurobiology, vol. 74, no. 5, pp. 301–320, 2004. View at Publisher · View at Google Scholar
  136. V. Bolivar and L. Flaherty, “A region on chromosome 15 controls intersession habituation in mice,” Journal of Neuroscience, vol. 23, no. 28, pp. 9435–9438, 2003. View at Google Scholar
  137. J. Gallinat, A. Ströhle, U. E. Lang et al., “Association of human hippocampal neurochemistry, serotonin transporter genetic variation, and anxiety,” NeuroImage, vol. 26, no. 1, pp. 123–131, 2005. View at Publisher · View at Google Scholar
  138. E. Maron, T. Nikopensius, S. Kõks et al., “Association study of 90 candidate gene polymorphisms in panic disorder,” Psychiatric Genetics, vol. 15, no. 1, pp. 17–24, 2005. View at Publisher · View at Google Scholar
  139. F. G. Graeff, M. C. Silveira, R. L. Nogueira, E. A. Audi, and R. M. W. Oliveira, “Role of the amygdala and periaqueductal gray in anxiety and panic,” Behavioural Brain Research, vol. 58, no. 1-2, pp. 123–131, 1993. View at Publisher · View at Google Scholar
  140. L. Groenink, M. J. V. Van Bogaert, J. Van Der Gugten, R. S. Oosting, and B. Olivier, “5-HT1A receptor and 5-HT1b receptor knockout mice in stress and anxiety paradigms,” Behavioural Pharmacology, vol. 14, no. 5-6, pp. 369–383, 2003. View at Google Scholar
  141. J. G. Hensler, “Serotonergic modulation of the limbic system,” Neuroscience and Biobehavioral Reviews, vol. 30, no. 2, pp. 203–214, 2006. View at Publisher · View at Google Scholar
  142. H. Kusserow, B. Davies, H. Hörtnagl et al., “Reduced anxiety-related behaviour in transgenic mice overexpressing serotonin1A receptors,” Molecular Brain Research, vol. 129, no. 1-2, pp. 104–116, 2004. View at Publisher · View at Google Scholar
  143. K. P. Lesch, “Neurotism and serotonin: a developmental genetic perspective,” in Behavioral Genetics in the Postgenomic Era, R. Plomin, J. DeFries, I. Craig, and P. McGuffin, Eds., pp. 389–423, American Psychological Association, Washington, DC, USA, 2002. View at Google Scholar
  144. K. P. Lesch, Y. Zeng, A. Reif, and L. Gutknecht, “Anxiety-related traits in mice with modified genes of the serotonergic pathway,” European Journal of Pharmacology, vol. 480, no. 1–3, pp. 185–204, 2003. View at Publisher · View at Google Scholar
  145. D. L. Murphy, A. Lerner, G. Rudnick, and K.-P. Lesch, “Serotonin transporter: gene, genetic disorders, and pharmacogenetics,” Molecular Interventions, vol. 4, no. 2, pp. 109–123, 2004. View at Publisher · View at Google Scholar
  146. A. Holmes, R. J. Yang, K.-P. Lesch, J. N. Crawley, and D. L. Murphy, “Mice lacking the serotonin transporter exhibit 5-HT1A receptor-mediated abnormalities in tests for anxiety-like behavior,” Neuropsychopharmacology, vol. 28, no. 12, pp. 2077–2088, 2003. View at Google Scholar
  147. D. L. Murphy, G. R. Uhl, A. Holmes et al., “Experimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disorders,” Genes, Brain and Behavior, vol. 2, no. 6, pp. 350–364, 2003. View at Publisher · View at Google Scholar
  148. S. Zhao, J. Edwards, J. Carroll et al., “Insertion mutation at the C-terminus of the serotonin transporter disrupts brain serotonin function and emotion-related behaviors in mice,” Neuroscience, vol. 140, no. 1, pp. 321–334, 2006. View at Publisher · View at Google Scholar
  149. R. Adamec, P. Burton, J. Blundell, D. L. Murphy, and A. Holmes, “Vulnerability to mild predator stress in serotonin transporter knockout mice,” Behavioural Brain Research, vol. 170, no. 1, pp. 126–140, 2006. View at Publisher · View at Google Scholar
  150. S. Zhang, T. Amstein, J. Shen, F. R. Brush, and H. K. Gershenfeld, “Molecular correlates of emotional learning using genetically selected rat lines,” Genes, Brain and Behavior, vol. 4, no. 2, pp. 99–109, 2005. View at Publisher · View at Google Scholar
  151. T. Mizuno, M. Aoki, Y. Shimada et al., “Gender difference in association between polymorphism of serotonin transporter gene regulatory region and anxiety,” Journal of Psychosomatic Research, vol. 60, no. 1, pp. 91–97, 2006. View at Publisher · View at Google Scholar
  152. A. Bertolino, G. Arciero, V. Rubino et al., “Variation of human amygdala response during threatening stimuli as a function of 5HTTLPR genotype and personality style,” Biological Psychiatry, vol. 57, no. 12, pp. 1517–1525, 2005. View at Publisher · View at Google Scholar
  153. A. R. Hariri, E. M. Drabant, and D. R. Weinberger, “Imaging genetics: perspectives from studies of genetically driven variation in serotonin function and corticolimbic affective processing,” Biological Psychiatry, vol. 59, no. 10, pp. 888–897, 2006. View at Publisher · View at Google Scholar
  154. D. J. Stein and H. Matsunaga, “Specific phobia: a disorder of fear conditioning and extinction,” CNS Spectrums, vol. 11, no. 4, pp. 248–251, 2006. View at Google Scholar
  155. A. Payton, L. Gibbons, Y. Davidson et al., “Influence of serotonin transporter gene polymorphisms on cognitive decline and cognitive abilities in a nondemented elderly population,” Molecular Psychiatry, vol. 10, no. 12, pp. 1133–1139, 2005. View at Publisher · View at Google Scholar
  156. A. Caspi, K. Sugden, T. E. Moffitt et al., “Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene,” Science, vol. 301, no. 5631, pp. 386–389, 2003. View at Publisher · View at Google Scholar
  157. N. A. Fox, K. E. Nichols, H. A. Henderson et al., “Evidence for a gene-environment interaction in predicting behavioral inhibition in middle childhood,” Psychological Science, vol. 16, no. 12, pp. 921–926, 2005. View at Publisher · View at Google Scholar
  158. A. V. Kalueff, D. F. Avgustinovich, N. N. Kudryavtseva, and D. L. Murphy, “BDNF in anxiety and depression,” Science, vol. 312, no. 5780, pp. 1598–1599, 2006. View at Publisher · View at Google Scholar
  159. S. Linnarsson, A. Björklund, and P. Ernfors, “Learning deficit in BDNF mutant mice,” European Journal of Neuroscience, vol. 9, no. 12, pp. 2581–2587, 1997. View at Publisher · View at Google Scholar
  160. S. Chourbaji, R. Hellweg, D. Brandis et al., “Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior,” Molecular Brain Research, vol. 121, no. 1-2, pp. 28–36, 2004. View at Publisher · View at Google Scholar
  161. A. Montkowski and F. Holsboer, “Intact spatial learning and memory in transgenic mice with reduced BDNF,” NeuroReport, vol. 8, no. 3, pp. 779–782, 1997. View at Publisher · View at Google Scholar
  162. O. Berton, C. A. McClung, R. J. DiLeone et al., “Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress,” Science, vol. 311, no. 5762, pp. 864–868, 2006. View at Publisher · View at Google Scholar
  163. F. Cirulli, A. Berry, F. Chiarotti, and E. Alleva, “Intrahippocampal administration of BDNF in adult rats affects short-term behavioral plasticity in the Morris water maze and performance in the elevated plus-maze,” Hippocampus, vol. 14, no. 7, pp. 802–807, 2004. View at Publisher · View at Google Scholar
  164. M. Alonso, P. Bekinschtein, M. Cammarota, M. R. M. Vianna, I. Izquierdo, and J. H. Medina, “Endogenous BDNF is required for long-term memory formation in the rat parietal cortex,” Learning and Memory, vol. 12, no. 5, pp. 504–510, 2005. View at Publisher · View at Google Scholar
  165. E. Koponen, V. Võikar, R. Riekki et al., “Transgenic mice overexpressing the full-length neurotrophin receptor trkB exhibit increased activation of the trkB-PLCγ pathway, reduced anxiety, and facilitated learning,” Molecular and Cellular Neuroscience, vol. 26, no. 1, pp. 166–181, 2004. View at Publisher · View at Google Scholar
  166. J. A. Gorski, S. A. Balogh, J. M. Wehner, and K. R. Jones, “Learning deficits in forebrain-restricted brain-derived neurotrophic factor mutant mice,” Neuroscience, vol. 121, no. 2, pp. 341–354, 2003. View at Publisher · View at Google Scholar
  167. J. Schulkin, M. A. Morgan, and J. B. Rosen, “A neuroendocrine mechanism for sustaining fear,” Trends in Neurosciences, vol. 28, no. 12, pp. 629–635, 2005. View at Publisher · View at Google Scholar
  168. D. G. Rainnie, R. Bergeron, T. J. Sajdyk, M. Patil, D. R. Gehlert, and A. Shekhar, “Corticotrophin releasing factor-induced synaptic plasticity in the amygdala translates stress into emotional disorders,” Journal of Neuroscience, vol. 24, no. 14, pp. 3471–3479, 2004. View at Publisher · View at Google Scholar
  169. A. Shekhar, W. Truitt, D. Rainnie, and T. Sajdyk, “Role of stress, corticotrophin releasing factor (CRF) and amygdala plasticity in chronic anxiety,” Stress, vol. 8, no. 4, pp. 209–219, 2005. View at Publisher · View at Google Scholar
  170. E. Kojro, R. Postina, C. Buro, C. Meiringer, K. Gehrig-Burger, and F. Fahrenholz, “The neuropeptide PACAP promotes the alpha-secretase pathway for processing the Alzheimer amyloid precursor protein,” FASEB Journal, vol. 20, no. 3, pp. 512–514, 2006. View at Google Scholar
  171. D. Kapfhamer, O. Valladares, Y. Sun et al., “Mutations in Rab3a alter circadian period and homeostatic response to sleep loss in the mouse,” Nature Genetics, vol. 32, no. 2, pp. 290–295, 2002. View at Publisher · View at Google Scholar
  172. S. Thakker-Varia, J. Alder, R. A. Crozier, M. R. Plummer, and I. B. Black, “Rab3A is required for brain-derived neurotrophic factor-induced synaptic plasticity: transcriptional analysis at the population and single-cell levels,” Journal of Neuroscience, vol. 21, no. 17, pp. 6782–6790, 2001. View at Google Scholar
  173. D. K. Binder and H. E. Scharfman, “Brain-derived neurotrophic factor,” Growth Factors, vol. 22, no. 3, pp. 123–131, 2004. View at Publisher · View at Google Scholar
  174. N. Francia, F. Cirulli, F. Chiarotti, A. Antonelli, L. Aloe, and E. Alleva, “Spatial memory deficits in middle-aged mice correlate with lower exploratory activity and a subordinate status: role of hippocampal neurotrophins,” European Journal of Neuroscience, vol. 23, no. 3, pp. 711–728, 2006. View at Publisher · View at Google Scholar
  175. L. Song, W. Che, W. Min-Wei, Y. Murakami, and K. Matsumoto, “Impairment of the spatial learning and memory induced by learned helplessness and chronic mild stress,” Pharmacology Biochemistry and Behavior, vol. 83, no. 2, pp. 186–193, 2006. View at Publisher · View at Google Scholar
  176. L. M. Rattiner, M. Davis, and K. J. Ressler, “Differential regulation of brain-derived neurotrophic factor transcripts during the consolidation of fear learning,” Learning and Memory, vol. 11, no. 6, pp. 727–731, 2004. View at Publisher · View at Google Scholar
  177. L. M. Rattiner, M. Davis, and K. J. Ressler, “Brain-derived neurotrophic factor in amygdala-dependent learning,” Neuroscientist, vol. 11, no. 4, pp. 323–333, 2005. View at Publisher · View at Google Scholar
  178. U. E. Lang, R. Hellweg, P. Kalus et al., “Association of a functional BDNF polymorphism and anxiety-related personality traits,” Psychopharmacology, vol. 180, no. 1, pp. 95–99, 2005. View at Publisher · View at Google Scholar
  179. J. A. Bueller, M. Aftab, S. Sen, D. Gomez-Hassan, M. Burmeister, and J.-K. Zubieta, “BDNF Val66Met allele is associated with reduced hippocampal volume in healthy subjects,” Biological Psychiatry, vol. 59, no. 9, pp. 812–815, 2006. View at Publisher · View at Google Scholar
  180. E. Dempster, T. Toulopoulou, C. McDonald et al., “Association between BDNF val66 met genotype and episodic memory,” American Journal of Medical Genetics, vol. 134 B, no. 1, pp. 73–75, 2005. View at Publisher · View at Google Scholar
  181. M. P. Mattson, S. Maudsley, and B. Martin, “BDNF and 5-HT: a dynamic duo in age-related neuronal plasticity and neurodegenerative disorders,” Trends in Neurosciences, vol. 27, no. 10, pp. 589–594, 2004. View at Publisher · View at Google Scholar
  182. M. Rios, E. K. Lambe, R. Liu et al., “Severe deficits in 5-HT2A-mediated neurotransmission in BDNF conditional mutant mice,” Journal of Neurobiology, vol. 66, no. 4, pp. 408–420, 2006. View at Publisher · View at Google Scholar
  183. J. A. Siuciak, C. Boylan, M. Fritsche, C. A. Altar, and R. M. Lindsay, “BDNF increases monoaminergic activity in rat brain following intracerebroventricular or intraparenchymal administration,” Brain Research, vol. 710, no. 1-2, pp. 11–20, 1996. View at Publisher · View at Google Scholar
  184. M. E. Szapacs, T. A. Mathews, L. Tessarollo, W. Ernest Lyons, L. A. Mamounas, and A. M. Andrews, “Exploring the relationship between serotonin and brain-derived neurotrophic factor: analysis of BDNF protein and extraneuronal 5-HT in mice with reduced serotonin transporter or BDNF expression,” Journal of Neuroscience Methods, vol. 140, no. 1-2, pp. 81–92, 2004. View at Publisher · View at Google Scholar
  185. A. Payton, “Investigating cognitive genetics and its implications for the treatment of cognitive deficit,” Genes, Brain and Behavior, vol. 5, 1, pp. 44–53, 2006. View at Publisher · View at Google Scholar
  186. R. F. Ren-Patterson, L. W. Cochran, A. Holmes et al., “Loss of brain-derived neurotrophic factor gene allele exacerbates brain monoamine deficiencies and increases stress abnormalities of serotonin transporter knockout mice,” Journal of Neuroscience Research, vol. 79, no. 6, pp. 756–771, 2005. View at Publisher · View at Google Scholar
  187. J. Kaufman, B.-Z. Yang, H. Douglas-Palumberi et al., “Social supports and serotonin transporter gene moderate depression in maltreated children,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 49, pp. 17316–17321, 2004. View at Publisher · View at Google Scholar