The impact of adolescent social isolation on dopamine D2 and cannabinoid CB1 receptors in the adult rat prefrontal cortex
- a Department of Neuroscience, Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, United States
- b Department of Psychological and Brain Sciences and the Gill Center, Indiana University, Bloomington, IN 47405, United States
Abstract
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 CB1 receptor antagonist. The patterning and abundance of D2 receptors in the PFC evolves concurrently with CB1 receptors through the period of adolescence. This evidence suggests that mature expression and/or surface distribution of D2 and CB1 receptors may be influenced by the adolescent social environment. We tested this hypothesis using electron microscopic immunolabeling to compare the distribution of CB1 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 CB1. There was no apparent change in the expression of CB1 or D2 receptors in presynaptic terminals. The D2 deficit therefore may be tempered by local CB1-mediated retrograde signaling. This suggests a biological mechanism whereby the adolescent social environment can persistently influence cortical dopaminergic activity and resultant behavior.
Highlights
- 2-AG, 2-arachidonoylglycerol;
- DAB, 3,3′-diaminobenzidine;
- PBS, phosphate-buffered saline;
- PFA,paraformaldehyde;
- PFC, prefrontal cortex;
- PPI, prepulse inhibition;
- PL, prelimbic;
- TBS, Tris-buffered saline;
- VTA, ventral tegmental area
Key words
- prefrontal cortex (PFC);
- schizophrenia;
- electron microscopy;
- dopamine;
- adolescence;
- isolation rearing
Figures and tables from this article:
- Fig. 1. Between-group planned comparisons at each level of prepulse volume show a significant difference in% PPI at the 6-dB prepulse level (t = −2.220, p < 0.05), indicating a significantly lower PPI in isolated rats than in socially-reared controls (∗p < 0.05, n = 9 per group, data are represented as mean ± S.E.M). Prepulse volume denotes the decibel level of the prepulse above background noise. Group-reared animals are represented by gray bars while isolates are represented by white in the histogram shown.
- Fig. 2. There is a significant decrease in dendritic D2 receptor expression in the PL of isolated rats relative to group-housed controls. (A–C) Dendrites of various sizes from socially-reared rats contain D2 immunogold (D2 de). In (C), a dendrite containing D2 immunogold is contacted by a D2 terminal (D2 te). (D–F) Dendrites from the PL of isolated rats contain qualitatively less D2 immunogold than group-housed controls. In (E), a D2 immunogold particle (black arrow) contacts the outer edge of the postsynaptic density of an asymmetric excitatory-type synapse formed by an unlabeled axon terminal (te). (G–I) Dendrites of isolation-reared rats contain significantly less total D2 (G) and cytoplasmic (H) immunogold per μm2 area relative to group-reared controls but the density of plasmalemmal D2 immunogold particles per μm membrane (I) does not significantly differ between groups (∗∗p < 0.005, n = 9 per group, data are represented as mean ± S.E.M). Scale bar = 500 nm.
- Fig. 3. There is no significant difference between group-reared (A, B) and isolated (C, D) rats in D2 receptor density in dendrites contacted by CB1-containing axon terminals. (A) An axon terminal containing CB1 immunoperoxidase reaction product (CB1 te) apposes two D2-immunogold labeled dendrites (D2 de). An axon terminal containing D2 immunogold (D2 te) also contacts both dendrites. (B) Both an unlabeled axon terminal (te) and a CB1 terminal contact a dendrite containing D2 immunogold. (C) A large CB1 axon terminal targets a D2-containing dendrite in the PL of an isolation-reared rat. (D) A CB1 immunoreactive axon terminal forms a symmetric inhibitory-type synaptic contact (white arrow) with a dendrite containing D2 immunogold. Scale bar = 500 nm.
- Fig. 4. Expression of dopamine D2 receptors is similar in dendritic spines of group-reared (A) and isolated (B) rats. (A) A D2-containing terminal (D2 te) forms a synapse with a dendritic spine expressing D2 (D2 sp). An apposing CB1 terminal contacts a D2 dendrite (D2 de). (B) An unlabeled terminal (te) forms an asymmetric excitatory-type contact with a spine containing D2 immunogold (D2 sp). In both animals, note the positioning of D2 immunogold opposite the postsynaptic density of the dendritic spines (dashed lines), consistent with dopaminergic input on spine necks (Freund et al., 1984). Scale bar = 500 nm.
- Fig. 5. Axon terminals containing CB1 immunoperoxidase were rarely dual labeled for D2 immunogold in both socially-reared (A) and isolation-reared (B) rats. (A) An axon terminal characterized by the abundant presence of synaptic vesicles contains both CB1 immunoperoxidase and D2 immunogold labeling (arrows). This axon terminal is adjacent to an unlabeled terminal (te) and a D2-dendrite (D2 de). (B) A CB1 axon terminal from an isolation-reared rat holds two D2-immunogold particles (arrows) and contacts an unlabeled dendrite (de). Scale bar = 500 nm.
- Table 1. Overall distribution of CB1 and D2 receptors is similar in neuronal profiles of isolated and socially reared rats. A total number of 3312 profiles were measured and compared between groups
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Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.
