Gonadal hormones-mediated effects on the stimulation of dopamine turnover in mesolimbic and nigrostriatal systems by cocaine- and amphetamine-regulated transcript (CART) peptide in male rats

Estradiol and testosterone modulated behavioral and neurochemical activities in the mesolimbic and nigrostriatal dopaminergic systems have been reported. We examined whether estradiol and testosterone affect stimulation of cocaine- and amphetamine-regulated transcript (CART) peptide in the mesolimbic and nigrostriatal dopaminergic systems in this study. Intracerebroventricular administration of CART peptide increased dopamine turnover in the nucleus accumbens and striatum in male rats. Stimulation of dopamine turnover in nucleus accumbens and striatum by CART peptide were found in intact male rats, but not in castrated male rats. This stimulation was restored in castrated male rats by testosterone or estradiol priming, or by treatment with the water-soluble form of estradiol, but not by treatment with the membrane-impermeable form of estradiol. Estradiol and testosterone antagonists blocked testosterone's effects, but only estradiol antagonist blocked estradiol's effects. Moreover, treatment of dihydrotestosterone also restored the stimulation in castrated male rats. This dihydrotestosterone's effect was blocked by a testosterone antagonist, but not by an estradiol antagonist. All of these findings indicate that gonadal hormones play a regulatory role in stimulation of CART peptide in mesolimbic and nigrostriatal dopaminergic systems, and suggest that acts through intracellular rather than extracellular mechanisms.