COCAINE‐INDUCED ALTERATIONS IN D2/D3 RECEPTOR FUNCTION IN MALE RATS WITH AND WITHOUT TESTOSTERONE REPLACEMENT

Abstract

Previous studies in our laboratory indicate that testosterone modulates cocaine-induced locomotor activity in the male rat. In this study, functional autoradiography was used to investigate cocaine modulation of D2/D3 receptors in male rats. Adult Sprague-Dawley rats were orchidectomized and received an empty (GDX) or testosterone-filled (GDX-T) silastic implant. A week later, they received a daily injection of saline or cocaine (15 mg/kg,i.p.) for 5 days. On day 13 they received another cocaine injection (15 mg/kg, i.p.). To determine D2/D3 receptor function, quinpirole-stimulated [35S] GTPγ S binding was assessed in the striatum (STR) and nucleus accumbens (NAc). GDX males showed higher levels of D2/D3 signal transduction in the STR and NAc compared to GDX-T males. When rats were injected with cocaine, we observed that only GDX-T males showed an increase in quinpirole-stimulated [35S] GTPγ S binding in these brain areas. The cocaine paradigm for our studies did not induce behavioral sensitization in GDX-T males but it did in GDX males, which did not show robust changes in D2/D3 function in the brain areas studied. These data indicate that D2/D3 function is modulated by testosterone in male rats and suggest an inhibitory role of D2/D3 in behavioral sensitization. This work was supported partially by NIH grants U54 NS3905 04 (NINDS/SNRP); SO6-GM08224 (MBRS/SCORE), RR03051 (NCRR/RCMI); and R25 GM61838 (MBRS/RISE)