Table of Contents
ISRN Psychiatry
Volume 2012, Article ID 451865, 9 pages
Research Article

Synergistic Effect between Maternal Infection and Adolescent Cannabinoid Exposure on Serotonin 5HT1A Receptor Binding in the Hippocampus: Testing the “Two Hit” Hypothesis for the Development of Schizophrenia

1Schizophrenia Research Institute, Sydney, NSW 2010, Australia
2Department of Psychiatry and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland
3Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW 2234, Australia
4Laboratory of Neuroimmunology, School of Psychology, The University of Newcastle Australia, Newcastle, NSW 2300, Australia
5School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia
6Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, NSW 2031, Australia

Received 15 March 2012; Accepted 10 April 2012

Academic Editors: B. Biancosino, C. M. Contreras, C. Eggers, and A. Michael

Copyright © 2012 Victoria S. Dalton et al. 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.


Infections during pregnancy and adolescent cannabis use have both been identified as environmental risk factors for schizophrenia. We combined these factors in an animal model and looked at their effects, alone and in combination, on serotonin 5 H T 1 A receptor binding ( 5 H T 1 A R ) binding longitudinally from late adolescence to adulthood. Pregnant rats were exposed to the viral mimic poly I:C on embryonic day 15. Adolescent offspring received daily injections of the cannabinoid HU210 for 14 days starting on postnatal day (PND) 35. Hippocampal and cortical 5 H T 1 A R binding was quantified autoradiographically using [3H]8-OH-DPAT, in late adolescent (PND 55), young adult (PND 65) and adult (PND 90) rats. Descendants of poly I:C treated rats showed significant increases of 15–18% in 5 H T 1 A R in the hippocampus (CA1) compared to controls at all developmental ages. Offspring of poly I:C treated rats exposed to HU210 during adolescence exhibited even greater elevations in 5 H T 1 A R (with increases of 44, 29, and 39% at PNDs 55, 65, and 90). No effect of HU210 alone was observed. Our results suggest a synergistic effect of prenatal infection and adolescent cannabinoid exposure on the integrity of the serotoninergic system in the hippocampus that may provide the neurochemical substrate for abnormal hippocampal-related functions relevant to schizophrenia.