Abstract
The mediodorsal thalamus (MD) and lateral hypothalamus (LH) are brain areas involved in motivational and emotional aspects of pleasurable behaviors such as feeding and drug addiction. Previous studies have shown that sex steroids modulate both behaviors, and although these areas contain sex steroid receptors, their role in mediating sex differences in addictive behavior has not been explored. We use functional autoradiography to investigate cocaine modulation of D2/D3 receptors in gonadectomized Sprague-Dawley male rats with (GDX-T) and without (GDX) testosterone replacement. Adult rats received a daily injection of saline or cocaine (15 mg/kg,i.p.) for 5 days, followed by 7 drug free days. A challenge injection of saline or cocaine (15 mg/kg,i.p.) was given on day 13. To determine D2/D3 receptor function, quinpirole-stimulated [35S] GTP γS binding was assessed in the LH and MD. Cocaine decreased D2/D3 signal transduction in the LH and MD of GDX-T males. However, quinpirole-stimulated [35S] GTPγS binding was increased in the LH of GDX males. No effect of cocaine was observed in the MD of GDX males. The same GDX-T males did not show cocaine-induced behavioral sensitization, suggesting that in these brain areas, D2/D3 receptors may enhance cocaine sensitization. Support Contributed By: NIH grants U54 NS3905 04 (NINDS/SNRP); SO6-GM08224 (MBRS/SCORE), RR03051 (NCRR/RCMI); and R25 GM61838 (MBRS/RISE).
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