THE IMPACT OF ADOLESCENT SOCIAL ISOLATION ON DOPAMINE D2 AND CANNABINOID CB1 RECEPTORS IN THE ADULT RAT PREFRONTAL CORTEX

Adolescent experiences of social deprivation result in profound and enduring perturbations in adult behavior, including impaired sensorimotor gating. The behavioral deficits induced by adolescent social isolation in rats can be ameliorated by antipsychotic drugs blocking dopamine D2 receptors in the prefrontal cortex (PFC) or by chronic administration of a cannabinoid CBI receptor antagonist. The patterning and abundance of D2 receptors in the PFC evolves concurrently with CBI receptors through the period of adolescence. This evidence suggests that mature expression and/or surface distribution of D2 and CBI receptors may be influenced by the adolescent social environment. We tested this hypothesis using electron microscopic immunolabeling to compare the distribution of CBI and D2 receptors in the PFC of adult male Sprague-Dawley rats that were isolated or socially reared throughout the adolescent transition period. Prepulse inhibition (PPI) of acoustic startle was assessed as a measure of sensorimotor gating. Social isolation reduced PPI and selectively decreased dendritic D2 immunogold labeling in the PFC. However, the decrease was only evident in dendrites that were not contacted by axon terminals containing CBI. There was no apparent change in the expression of CBI or D2 receptors in presynaptic terminals. The D2 deficit therefore may be tempered by local CBI-mediated retrograde signaling. This suggests a biological mechanism whereby the adolescent social environment can persistently influence cortical dopaminergic activity and resultant behavior. (C) 2013 IBRO. Published by Elsevier Ltd. All rights reserved.