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Volume 2007 (2007), Article ID 30873, 11 pages
http://dx.doi.org/10.1155/2007/30873
Review Article

The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

1Department of Psychology, The Brain and Behavior Research Center, University of Haifa, Haifa 31905, Israel
2Department of Neurobiology and Ethology, The Brain and Behavior Research Center, Faculty of Science and Science Education, University of Haifa, Haifa 31905, Israel

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

Academic Editor: Georges Chapouthier

Copyright © 2007 Irit Akirav and Mouna Maroun. 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. D. S. Charney, “Psychobiological mechanism of resilience and vulnerability: implications for successful adaptation to extreme stress,” American Journal of Psychiatry, vol. 161, no. 2, pp. 195–216, 2004. View at Publisher · View at Google Scholar
  2. D. E. Berman and Y. Dudai, “Memory extinction, learning anew, and learning the new: dissociations in the molecular machinery of learning in cortex,” Science, vol. 291, no. 5512, pp. 2417–2419, 2001. View at Publisher · View at Google Scholar
  3. M. E. Bouton and J. B. Nelson, “Context-specificity of target versus feature inhibition in a feature-negative discrimination,” Journal of Experimental Psychology: Animal Behavior Processes, vol. 20, no. 1, pp. 51–65, 1994. View at Publisher · View at Google Scholar
  4. K. M. Myers and M. Davis, “Behavioral and neural analysis of extinction,” Neuron, vol. 36, no. 4, pp. 567–584, 2002. View at Publisher · View at Google Scholar
  5. R. A. Rescorla, “Preservation of pavlovian associations through extinction,” Quarterly Journal of Experimental Psychology Section B: Comparative and Physiological Psychology, vol. 49, no. 3, pp. 245–258, 1996.
  6. D. S. Charney, A. Y. Deutch, J. H. Krystal, S. M. Southwick, and M. Davis, “Psychobiologic mechanisms of posttraumatic stress disorder,” Archives of General Psychiatry, vol. 50, no. 4, pp. 295–305, 1993.
  7. A. J. Fyer, “Current approaches to etiology and pathophysiology of specific phobia,” Biological Psychiatry, vol. 44, no. 12, pp. 1295–1304, 1998. View at Publisher · View at Google Scholar
  8. J. M. Gorman, “Treating generalized anxiety disorder,” Journal of Clinical Psychiatry, vol. 64, 2, pp. 24–29, 2003.
  9. R. A. Rescorla, “Experimental extinction,” in Handbook of Contemporary Learning Theories, R. R. Mowrer and S. Klein, Eds., pp. 119–154, Erlbaum, Mahwah, NJ, USA, 2001.
  10. G. J. Quirk, “Memory for extinction of conditioned fear is long-lasting and persists following spontaneous recovery,” Learning and Memory, vol. 9, no. 6, pp. 402–407, 2002. View at Publisher · View at Google Scholar
  11. R. A. Rescorla and C. D. Heth, “Reinstatement of fear to an extinguished conditioned stimulus,” Journal of Experimental Psychology: Animal Behavior Processes, vol. 1, no. 1, pp. 88–96, 1975. View at Publisher · View at Google Scholar
  12. M. E. Bouton and R. C. Bolles, “Role of conditioned contextual stimuli in reinstatement of extinguished fear,” Journal of Experimental Psychology: Animal Behavior Processes, vol. 5, no. 4, pp. 368–378, 1979. View at Publisher · View at Google Scholar
  13. M. E. Bouton and D. A. King, “Contextual control of the extinction of conditioned fear: tests for the associative value of the context,” Journal of Experimental Psychology: Animal Behavior Processes, vol. 9, no. 3, pp. 248–265, 1983. View at Publisher · View at Google Scholar
  14. M. Eisenberg, T. Kobilo, D. E. Berman, and Y. Dudai, “Stability of retrieved memory: inverse correlation with trace dominance,” Science, vol. 301, no. 5636, pp. 1102–1104, 2003. View at Publisher · View at Google Scholar
  15. B. S. McEwen, “The brain is an important target of adrenal steroid actions: a comparison of synthetic and natural steroids,” Annals of the New York Academy of Sciences, vol. 823, pp. 201–213, 1997. View at Publisher · View at Google Scholar
  16. A. Baum and D. M. Posluszny, “Health psychology: mapping biobehavioral contributions to health and illness,” Annual Review of Psychology, vol. 50, pp. 137–163, 1999. View at Publisher · View at Google Scholar
  17. W. A. Falls, M. J. D. Miserendino, and M. Davis, “Extinction of fear-potentiated startle: blockade by infusion of an NMDA antagonist into the amygdala,” The Journal of Neuroscience, vol. 12, no. 3, pp. 854–863, 1992.
  18. M. A. Morgan and J. E. LeDoux, “Differential contribution of dorsal and ventral medial prefrontal cortex to the acquisition and extinction of conditioned fear in rats,” Behavioral Neuroscience, vol. 109, no. 4, pp. 681–688, 1995. View at Publisher · View at Google Scholar
  19. G. J. Quirk, G. K. Russo, J. L. Barron, and K. Lebron, “The role of ventromedial prefrontal cortex in the recovery of extinguished fear,” The Journal of Neuroscience, vol. 20, no. 16, pp. 6225–6231, 2000.
  20. J. Prickaerts and T. Steckler, “Effects of glucocorticoids on emotion and cognitive processes in animals,” in Handbook of Stress and the Brain, T. S. Steckler, N. H. Kalin, and J. M. H. M. Ruel, Eds., pp. 359–385, Elsevier, Amsterdam, The Netherlands, 2005.
  21. L. Xu, R. Anwyl, and M. J. Rowan, “Behavioural stress facilitates the induction of long-term depression in the hippocampus,” Nature, vol. 387, no. 6632, pp. 497–500, 1997. View at Publisher · View at Google Scholar
  22. L. Xu, R. Anwyl, and M. J. Rowan, “Spatial exploration induces a persistent reversal of long-term potentiation in rat hippocampus,” Nature, vol. 394, no. 6696, pp. 891–894, 1998. View at Publisher · View at Google Scholar
  23. A. Kavushansky and G. Richter-Levin, “Effects of stress and corticosterone on activity and plasticity in the amygdala,” Journal of Neuroscience Research, vol. 84, no. 7, pp. 1580–1587, 2006. View at Publisher · View at Google Scholar
  24. M. Maroun and G. Richter-Levin, “Exposure to acute stress blocks the induction of long-term potentiation of the amygdala-prefrontal cortex pathway in vivo,” The Journal of Neuroscience, vol. 23, no. 11, pp. 4406–4409, 2003.
  25. A. Izquierdo, C. L. Wellman, and A. Holmes, “Brief uncontrollable stress causes dendritic retraction in infralimbic cortex and resistance to fear extinction in mice,” The Journal of Neuroscience, vol. 26, no. 21, pp. 5733–5738, 2006. View at Publisher · View at Google Scholar
  26. J. Shumake, D. Barrett, and F. Gonzalez-Lima, “Behavioral characteristics of rats predisposed to learned helplessness: reduced reward sensitivity, increased novelty seeking, and persistent fear memories,” Behavioural Brain Research, vol. 164, no. 2, pp. 222–230, 2005. View at Publisher · View at Google Scholar
  27. J. Kellett and L. Kokkinidis, “Extinction deficit and fear reinstatement after electrical stimulation of the amygdala: implications for kindling-associated fear and anxiety,” Neuroscience, vol. 127, no. 2, pp. 277–287, 2004. View at Publisher · View at Google Scholar
  28. P. S. A. Moreira, K. G. T. Pulman, and T. G. Pottinger, “Extinction of a conditioned response in rainbow trout selected for high or low responsiveness to stress,” Hormones and Behavior, vol. 46, no. 4, pp. 450–457, 2004. View at Publisher · View at Google Scholar
  29. M. I. Cordero, C. Venero, N. D. Kruyt, and C. Sandi, “Prior exposure to a single stress session facilitates subsequent contextual fear conditioning in rats: evidence for a role of corticosterone,” Hormones and Behavior, vol. 44, no. 4, pp. 338–345, 2003. View at Publisher · View at Google Scholar
  30. T. J. Shors, C. Weiss, and R. F. Thompson, “Stress-induced facilitation of classical conditioning,” Science, vol. 257, no. 5069, pp. 537–539, 1992. View at Publisher · View at Google Scholar
  31. A. V. Beylin and T. J. Shors, “Stress enhances excitatory trace eyeblink conditioning and opposes acquisition of inhibitory conditioning,” Behavioral Neuroscience, vol. 112, no. 6, pp. 1327–1338, 1998. View at Publisher · View at Google Scholar
  32. T. J. Shors, “Acute stress rapidly and persistently enhances memory formation in the male rat,” Neurobiology of Learning and Memory, vol. 75, no. 1, pp. 10–29, 2001. View at Publisher · View at Google Scholar
  33. P. A. Rodríguez Manzanares, N. A. Isoardi, H. F. Carrer, and V. A. Molina, “Previous stress facilitates fear memory, attenuates GABAergic inhibition, and increases synaptic plasticity in the rat basolateral amygdala,” The Journal of Neuroscience, vol. 25, no. 38, pp. 8725–8734, 2005. View at Publisher · View at Google Scholar
  34. V. Rau, J. P. DeCola, and M. S. Fanselow, “Stress-induced enhancement of fear learning: an animal model of posttraumatic stress disorder,” Neuroscience and Biobehavioral Reviews, vol. 29, no. 8, pp. 1207–1223, 2005. View at Publisher · View at Google Scholar
  35. E. R. De Kloet, E. Vreugdenhil, M. S. Oitzl, and M. Joëls, “Brain corticosteroid receptor balance in health and disease,” Endocrine Reviews, vol. 19, no. 3, pp. 269–301, 1998. View at Publisher · View at Google Scholar
  36. E. R. De Kloet, M. S. Oitzl, and M. Joëls, “Stress and cognition: are corticosteroids good or bad guys?” Trends in Neurosciences, vol. 22, no. 10, pp. 422–426, 1999. View at Publisher · View at Google Scholar
  37. B. Roozendaal, “Systems mediating acute glucocorticoid effects on memory consolidation and retrieval,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 27, no. 8, pp. 1213–1223, 2003. View at Publisher · View at Google Scholar
  38. G. L. Kovacs, G. Telegdy, and K. Lissak, “Dose dependent action of corticosteroids on brain serotonin content and passive avoidance behavior,” Hormones and Behavior, vol. 8, no. 2, pp. 155–165, 1977. View at Publisher · View at Google Scholar
  39. J. F. Flood, D. Vidal, E. L. Bennett, A. E. Orme, S. Vasquez, and M. E. Jarvik, “Memory facilitating and anti-amnesic effects of corticosteroids,” Pharmacology Biochemistry and Behavior, vol. 8, no. 1, pp. 81–87, 1978. View at Publisher · View at Google Scholar
  40. B. Roozendaal and J. L. McGaugh, “Amygdaloid nuclei lesions differentially affect glucocorticoid-induced memory enhancement in an inhibitory avoidance task,” Neurobiology of Learning and Memory, vol. 65, no. 1, pp. 1–8, 1996. View at Publisher · View at Google Scholar
  41. C. R. Pugh, D. Tremblay, M. Fleshner, and J. W. Rudy, “A selective role for corticosterone in contextual-fear conditioning,” Behavioral Neuroscience, vol. 111, no. 3, pp. 503–511, 1997. View at Publisher · View at Google Scholar
  42. C. Sandi, M. Loscertales, and C. Guaza, “Experience-dependent facilitating effect of corticosterone on spatial memory formation in the water maze,” European Journal of Neuroscience, vol. 9, no. 4, pp. 637–642, 1997. View at Publisher · View at Google Scholar
  43. M. I. Cordero and C. Sandi, “A role for brain glucocorticoid receptors in contextual fear conditioning: dependence upon training intensity,” Brain Research, vol. 786, no. 1-2, pp. 11–17, 1998. View at Publisher · View at Google Scholar
  44. G. K. Hui, I. R. Figueroa, B. S. Poytress, B. Roozendaal, J. L. McGaugh, and N. M. Weinberger, “Memory enhancement of classical fear conditioning by post-training injections of corticosterone in rats,” Neurobiology of Learning and Memory, vol. 81, no. 1, pp. 67–74, 2004. View at Publisher · View at Google Scholar
  45. J. J. Kim and D. M. Diamond, “The stressed hippocampus, synaptic plasticity and lost memories,” Nature Reviews Neuroscience, vol. 3, no. 6, pp. 453–462, 2002. View at Publisher · View at Google Scholar
  46. J. L. McGaugh, “The amygdala modulates the consolidation of memories of emotionally arousing experiences,” Annual Review of Neuroscience, vol. 27, pp. 1–28, 2004. View at Publisher · View at Google Scholar
  47. J. L. McGaugh, “Memory consolidation and the amygdala: a systems perspective,” Trends in Neurosciences, vol. 25, no. 9, pp. 456–461, 2002. View at Publisher · View at Google Scholar
  48. D. Paré, “Role of the basolateral amygdala in memory consolidation,” Progress in Neurobiology, vol. 70, no. 5, pp. 409–420, 2003. View at Publisher · View at Google Scholar
  49. J. G. Pelletier and D. Paré, “Role of amygdala oscillations in the consolidation of emotional memories,” Biological Psychiatry, vol. 55, no. 6, pp. 559–562, 2004. View at Publisher · View at Google Scholar
  50. T. Seidenbecher, K. G. Reymann, and D. Balschun, “A post-tetanic time window for the reinforcement of long-term potentiation by appetitive and aversive stimuli,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 4, pp. 1494–1499, 1997. View at Publisher · View at Google Scholar
  51. 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
  52. S. Maren, “Long-term potentiation in the amygdala: a mechanism for emotional learning and memory,” Trends in Neurosciences, vol. 22, no. 12, pp. 561–567, 1999. View at Publisher · View at Google Scholar
  53. K. Nader, G. E. Schafe, and J. E. Le Doux, “Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval,” Nature, vol. 406, no. 6797, pp. 722–726, 2000. View at Publisher · View at Google Scholar
  54. K. T. Lu, D. L. Walker, and M. Davis, “Mitogen-activated protein kinase cascade in the basolateral nucleus of amygdala is involved in extinction of fear-potentiated startle,” The Journal of Neuroscience, vol. 21, no. 16, p. RC162, 2001.
  55. H. Lee and J. J. Kim, “Amygdalar NMDA receptors are critical for new fear learning in previously fear-conditioned rats,” The Journal of Neuroscience, vol. 18, no. 20, pp. 8444–8454, 1998.
  56. C.-H. Lin, C.-C. Lee, and P.-W. Gean, “Involvement of a calcineurin cascade in amygdala depotentiation and quenching of fear memory,” Molecular Pharmacology, vol. 63, no. 1, pp. 44–52, 2003. View at Publisher · View at Google Scholar
  57. D. Anglada-Figueroa and G. J. Quirk, “Lesions of the basal amygdala block expression of conditioned fear but not extinction,” The Journal of Neuroscience, vol. 25, no. 42, pp. 9680–9685, 2005. View at Publisher · View at Google Scholar
  58. D. L. Walker, K. J. Ressler, K.-T. Lu, and M. Davis, “Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats,” The Journal of Neuroscience, vol. 22, no. 6, pp. 2343–2351, 2002.
  59. L. Ledgerwood, R. Richardson, and J. Cranney, “Effects of D-cycloserine on extinction of conditioned freezing,” Behavioral Neuroscience, vol. 117, no. 2, pp. 341–349, 2003. View at Publisher · View at Google Scholar
  60. R. M. Sullivan, “Hemispheric asymmetry in stress processing in rat prefrontal cortex and the role of mesocortical dopamine,” Stress, vol. 7, no. 2, pp. 131–143, 2004.
  61. H. J. Groenewegen and H. B. M. Uylings, “The prefrontal cortex and the integration of sensory, limbic and autonomic information,” Progress in Brain Research, vol. 126, pp. 3–28, 2000. View at Publisher · View at Google Scholar
  62. S. J. Spencer, K. M. Buller, and T. A. Day, “Medial prefrontal cortex control of the paraventricular hypothalamic nucleus response to psychological stress: possible role of the bed nucleus of the stria terminalis,” The Journal of Comparative Neurology, vol. 481, no. 4, pp. 363–376, 2005. View at Publisher · View at Google Scholar
  63. R. M. Sullivan and A. Gratton, “Prefrontal cortical regulation of hypothalamic-pituitary-adrenal function in the rat and implications for psychopathology: side matters,” Psychoneuroendocrinology, vol. 27, no. 1-2, pp. 99–114, 2002. View at Publisher · View at Google Scholar
  64. M. A. Morgan, L. M. Romanski, and J. E. LeDoux, “Extinction of emotional learning: contribution of medial prefrontal cortex,” Neuroscience Letters, vol. 163, no. 1, pp. 109–113, 1993. View at Publisher · View at Google Scholar
  65. E. Santini, H. Ge, K. Ren, S. Peña de Ortiz, and G. J. Quirk, “Consolidation of fear extinction requires protein synthesis in the medial prefrontal cortex,” The Journal of Neuroscience, vol. 24, no. 25, pp. 5704–5710, 2004. View at Publisher · View at Google Scholar
  66. M. R. Milad and G. J. Quirk, “Neurons in medial prefrontal cortex signal memory for fear extinction,” Nature, vol. 420, no. 6911, pp. 70–74, 2002. View at Publisher · View at Google Scholar
  67. M. R. Milad, I. Vidal-Gonzalez, and G. J. Quirk, “Electrical stimulation of medial prefrontal cortex reduces conditioned fear in a temporally specific manner,” Behavioral Neuroscience, vol. 118, no. 2, pp. 389–394, 2004. View at Publisher · View at Google Scholar
  68. C. Herry and R. Garcia, “Prefrontal cortex long-term potentiation, but not long-term depression, is associated with the maintenance of extinction of learned fear in mice,” The Journal of Neuroscience, vol. 22, no. 2, pp. 577–583, 2002.
  69. C. Herry and R. Garcia, “Behavioral and paired-pulse facilitation analyses of long-lasting depression at excitatory synapses in the medial prefrontal cortex in mice,” Behavioural Brain Research, vol. 146, no. 1-2, pp. 89–96, 2003. View at Publisher · View at Google Scholar
  70. E. A. Phelps, M. R. Delgado, K. I. Nearing, and J. E. LeDoux, “Extinction learning in humans: role of the amygdala and vmPFC,” Neuron, vol. 43, no. 6, pp. 897–905, 2004. View at Publisher · View at Google Scholar
  71. J. D. Bremner, L. H. Staib, D. Kaloupek, S. M. Southwick, R. Soufer, and D. S. Charney, “Neural correlates of exposure to traumatic pictures and sound in Vietnam combat veterans with and without posttraumatic stress disorder: a positron emission tomography study,” Biological Psychiatry, vol. 45, no. 7, pp. 806–816, 1999. View at Publisher · View at Google Scholar
  72. A. D. Miracle, M. F. Brace, K. D. Huyck, S. A. Singler, and C. L. Wellman, “Chronic stress impairs recall of extinction of conditioned fear,” Neurobiology of Learning and Memory, vol. 85, no. 3, pp. 213–218, 2006. View at Publisher · View at Google Scholar
  73. B. M. Elzinga and J. D. Bremner, “Are the neural substrates of memory the final common pathway in posttraumatic stress disorder (PTSD)?” Journal of Affective Disorders, vol. 70, no. 1, pp. 1–17, 2002. View at Publisher · View at Google Scholar
  74. I. P. Pavlov, Conditioned Reflexes: An Investigation of the Physiological Activity of the Cerebral Cortex, Oxford University Press, London, UK, 1927.
  75. J. A. Rosenkranz and A. A. Grace, “Cellular mechanisms of infralimbic and prelimbic prefrontal cortical inhibition and dopaminergic modulation of basolateral amygdala neurons in vivo,” The Journal of Neuroscience, vol. 22, no. 1, pp. 324–337, 2002.
  76. A. J. McDonald, F. Mascagni, and L. Guo, “Projections of the medial and lateral prefrontal cortices to the amygdala: a Phaseolus vulgaris leucoagglutinin study in the rat,” Neuroscience, vol. 71, no. 1, pp. 55–75, 1996. View at Publisher · View at Google Scholar
  77. D. Paré and Y. Smith, “The intercalated cell masses project to the central and medial nuclei of the amygdala in cats,” Neuroscience, vol. 57, no. 4, pp. 1077–1090, 1993. View at Publisher · View at Google Scholar
  78. S. Royer, M. Martina, and D. Paré, “An inhibitory interface gates impulse traffic between the input and output stations of the amygdala,” The Journal of Neuroscience, vol. 19, no. 23, pp. 10575–10583, 1999.
  79. A. Pinto and S. R. Sesack, “Prefrontal cortex projection to the rat amygdala: ultrastructural relationship to dopamine D1 and D2 receptors,” Abstracts - Society for Neuroscience, vol. 28, p. 587.6, 2002.
  80. D. Paré, G. J. Quirk, and J. E. Ledoux, “New vistas on amygdala networks in conditioned fear,” Journal of Neurophysiology, vol. 92, no. 1, pp. 1–9, 2004.
  81. M. Takagi and C. Yamamoto, “The long-lasting inhibition recorded in vitro from the lateral nucleus of the amygdala,” Brain Research, vol. 206, no. 2, pp. 474–478, 1981. View at Publisher · View at Google Scholar
  82. M. S. Washburn and H. C. Moises, “Electrophysiological and morphological properties of rat basolateral amygdaloid neurons in vitro,” The Journal of Neuroscience, vol. 12, no. 10, pp. 4066–4079, 1992.
  83. M. S. Washburn and H. C. Moises, “Inhibitory responses of rat basolateral amygdaloid neurons recorded in vitro,” Neuroscience, vol. 50, no. 4, pp. 811–830, 1992. View at Publisher · View at Google Scholar
  84. D. L. Niehoff and M. J. Kuhar, “Benzodiazepine receptors: localization in rat amygdala,” The Journal of Neuroscience, vol. 3, no. 10, pp. 2091–2097, 1983.
  85. J. Scheel-Kruger and E. N. Petersen, “Anticonflict effect of the benzodiazepines mediated by a GABAergic mechanism in the amygdala,” European Journal of Pharmacology, vol. 82, no. 1-2, pp. 115–116, 1982. View at Publisher · View at Google Scholar
  86. E. N. Petersen, C. Braestrup, and J. Scheel-Kruger, “Evidence that the anticonflict effect of midazolam in amgydala is mediated by the specific benzodiazepine receptors,” Neuroscience Letters, vol. 53, no. 3, pp. 285–288, 1985. View at Publisher · View at Google Scholar
  87. J. Muller, K. P. Corodimas, Z. Fridel, and J. E. LeDoux, “Functional inactivation of the lateral and basal nuclei of the amygdala by muscimol infusion prevents fear conditioning to an explicit conditioned stimulus and to contextual stimuli,” Behavioral Neuroscience, vol. 111, no. 4, pp. 683–691, 1997. View at Publisher · View at Google Scholar
  88. A. M. Jasnow and K. L. Huhman, “Activation of GABAA receptors in the amygdala blocks the acquisition and expression of conditioned defeat in Syrian hamsters,” Brain Research, vol. 920, no. 1-2, pp. 142–150, 2001. View at Publisher · View at Google Scholar
  89. S. K. Sanders and A. Shekhar, “Blockade of GABAA receptors in the region of the anterior basolateral amygdala of rats elicits increases in heart rate and blood pressure,” Brain Research, vol. 567, no. 1, pp. 101–110, 1991. View at Publisher · View at Google Scholar
  90. 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
  91. J. A. Harris and R. F. Westbrook, “Evidence that GABA transmission mediates context-specific extinction of learned fear,” Psychopharmacology, vol. 140, no. 1, pp. 105–115, 1998. View at Publisher · View at Google Scholar
  92. G. Marsicano, C. T. Wotjak, S. C. Azad, et al., “The endogenous cannabinoid system controls extinction of aversive memories,” Nature, vol. 418, no. 6897, pp. 530–534, 2002. View at Publisher · View at Google Scholar
  93. J. L. McGaugh, C. Castellano, and J. Brioni, “Picrotoxin enhances latent extinction of conditioned fear,” Behavioral Neuroscience, vol. 104, no. 2, pp. 264–267, 1990. View at Publisher · View at Google Scholar
  94. M. E. Pereira, C. Dalmaz, R. M. Rosat, and I. Izquierdo, “Diazepam blocks the interfering effect of post-training behavioral manipulations on retention of a shuttle avoidance task,” Psychopharmacology, vol. 94, no. 3, pp. 402–404, 1988. View at Publisher · View at Google Scholar
  95. M. E. Pereira, R. Rosat, C. H. Huang, M. G. C. Godoy, and I. Izquierdo, “Inhibition by diazepam of the effect of additional training and of extinction on the retention of shuttle avoidance behavior in rats,” Behavioral Neuroscience, vol. 103, no. 1, pp. 202–205, 1989. View at Publisher · View at Google Scholar
  96. J. R. Stowell, G. G. Berntson, and M. Sarter, “Attenuation of the bidirectional effects of chlordiazepoxide and FG 7142 on conditioned response suppression and associated cardiovascular reactivity by loss of cortical cholinergic inputs,” Psychopharmacology, vol. 150, no. 2, pp. 141–149, 2000. View at Publisher · View at Google Scholar
  97. 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
  98. J. H. Williams, J. A. Gray, J. Sinden, C. Buckland, and J. N. P. Rawlins, “Effects of GABAergic drugs, fornicotomy, hippocampectomy and septal lesions on the extinction of a discrete-trial fixed ratio 5 lever-press response,” Behavioural Brain Research, vol. 41, no. 2, pp. 129–150, 1990. View at Publisher · View at Google Scholar
  99. S. C. Azad, K. Monory, G. Marsicano, et al., “Circuitry for associative plasticity in the amygdala involves endocannabinoid signaling,” The Journal of Neuroscience, vol. 24, no. 44, pp. 9953–9961, 2004. View at Publisher · View at Google Scholar
  100. 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,” The Journal of Neuroscience, vol. 25, no. 2, pp. 502–506, 2005. View at Publisher · View at Google Scholar
  101. D. A. Overton, “Basic mechanisms of state-dependent learning,” Psychopharmacology Bulletin, vol. 14, no. 1, pp. 67–68, 1978.
  102. M. Davis and K. M. Myers, “The role of glutamate and gamma-aminobutyric acid in fear extinction: clinical implications for exposure therapy,” Biological Psychiatry, vol. 52, no. 10, pp. 998–1007, 2002. View at Publisher · View at Google Scholar
  103. R. Garcia, R.-M. Vouimba, M. Baudry, and R. F. Thompson, “The amygdala modulates prefrontal cortex activity relative to conditioned fear,” Nature, vol. 402, no. 6759, pp. 294–296, 1999. View at Publisher · View at Google Scholar
  104. J. E. LeDoux, “Emotion circuits in the brain,” Annual Review of Neuroscience, vol. 23, pp. 155–184, 2000. View at Publisher · View at Google Scholar
  105. J. J. Radley and J. H. Morrison, “Repeated stress and structural plasticity in the brain,” Ageing Research Reviews, vol. 4, no. 2, pp. 271–287, 2005. View at Publisher · View at Google Scholar
  106. H. T. Blair, G. E. Schafe, E. P. Bauer, S. M. Rodrigues, and J. E. LeDoux, “Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning,” Learning and Memory, vol. 8, no. 5, pp. 229–242, 2001. View at Publisher · View at Google Scholar
  107. A. Pitkanen, L. Stefanacci, C. R. Farb, G.-G. Go, J. E. LeDoux, and D. G. Amaral, “Intrinsic connections of the rat amygdaloid complex: projections originating in the lateral nucleus,” The Journal of Comparative Neurology, vol. 356, no. 2, pp. 288–310, 1995. View at Publisher · View at Google Scholar
  108. A. Pitkänen, V. Savander, and J. E. LeDoux, “Organization of intra-amygdaloid circuitries in the rat: an emerging framework for understanding functions of the amygdala,” Trends in Neurosciences, vol. 20, no. 11, pp. 517–523, 1997. View at Publisher · View at Google Scholar
  109. T. S. Gray, M. E. Carney, and D. J. Magnuson, “Direct projections from the central amygdaloid nucleus to the hypothalamic paraventricular nucleus: possible role in stress-induced adrenocorticotropin release,” Neuroendocrinology, vol. 50, no. 4, pp. 433–446, 1989.
  110. L. M. Shin, P. J. Whalen, R. K. Pitman, et al., “An fMRI study of anterior cingulate function in posttraumatic stress disorder,” Biological Psychiatry, vol. 50, no. 12, pp. 932–942, 2001. View at Publisher · View at Google Scholar
  111. 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.
  112. L. M. Shin, R. J. McNally, S. M. Kosslyn, et al., “Regional cerebral blood flow during script-driven imagery in childhood sexual abuse-related PTSD: a PET investigation,” American Journal of Psychiatry, vol. 156, no. 4, pp. 575–584, 1999.
  113. L. M. Shin, S. P. Orr, M. A. Carson, et al., “Regional cerebral blood flow in the amygdala and medial prefrontal cortex during traumatic imagery in male and female Vietnam veterans with PTSD,” Archives of General Psychiatry, vol. 61, no. 2, pp. 168–176, 2004. View at Publisher · View at Google Scholar
  114. I. Liberzon, S. F. Taylor, R. Amdur, et al., “Brain activation in PTSD in response to trauma-related stimuli,” Biological Psychiatry, vol. 45, no. 7, pp. 817–826, 1999. View at Publisher · View at Google Scholar
  115. S. L. Rauch, P. J. Whalen, L. M. Shin, et al., “Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study,” Biological Psychiatry, vol. 47, no. 9, pp. 769–776, 2000. View at Publisher · View at Google Scholar
  116. H. Kim, L. H. Somerville, T. Johnstone, A. L. Alexander, and P. J. Whalen, “Inverse amygdala and medial prefrontal cortex responses to surprised faces,” Neuroreport, vol. 14, no. 18, pp. 2317–2322, 2003. View at Publisher · View at Google Scholar
  117. D. D. Dougherty, S. L. Rauch, T. Deckersbach, et al., “Ventromedial prefrontal cortex and amygdala dysfunction during an anger induction positron emission tomography study in patients with major depressive disorder with anger attacks,” Archives of General Psychiatry, vol. 61, no. 8, pp. 795–804, 2004. View at Publisher · View at Google Scholar