Sex-differences in the effect of estradiol on cocaine-induced dopamine release: Role of selective estrogen receptors
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Women are more prone to escalating drug taking habits and relapse of addiction than men (Perry, Westenbroek & Becker 2011). Previous research shows that estradiol modulates this difference in clinical research and rodent models, through actions on mesolimbic dopamine (DA) systems (Yoest, Cummings & Becker 2015). Our lab has shown that estradiol enhances effects of cocaine on DA release in the Nucleus Accumbens (NAcc) of females and not males. The specific estradiol receptor modulating this effect is not known. To measure dopamine release in response to cocaine, we used Fast-Scan Cyclic Voltammetry (FSCV) after treating animals with either pyrazole propyl triol (PPT), an ER-selective agonist, diarylpropionitrile (DPN), an ER-selective agonist, or the non-selective agonist, estradiol benzoate (EB). Acute EB treatment significantly increased effects of cocaine on stimulated DA release in NAcc of females but not males, consistent with previous lab findings. EB significantly increased effects of cocaine on stimulated DA release in NAcc of females more than PPT but not DPN. Males treated with PPT show enhanced effect of cocaine on DA reuptake. We conclude that ER modulates effects of cocaine on dopamine reuptake in males, and ER modulates effects of cocaine on dopamine release in females.