Sex Differences in Dopamine Release in Nucleus Accumbens and Dorsal Striatum Determined by Chronic Fast-Scan Cyclic Voltammetry: Effects of Social Housing and Repeated Stimulation.

We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation-induced (ES; 60 Hz) DA release was recorded in the NAc of single- or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than that in males. Finally, DA release following ES of the medial forebrain bundle at 60 Hz was studied over 4 weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, and sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo.

Sex Differences in Dopamine Release in Nucleus Accumbens and Dorsal Striatum Determined by Chronic Fast Scan Cyclic Voltammetry: Effects of social housing and repeated stimulation.

We investigated sex differences in dopamine (DA) release in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) using a chronic 16-channel carbon fiber electrode and fast-scan cyclic voltammetry (FSCV). Electrical stimulation (ES; 60Hz) induced DA release was recorded in the NAc of single or pair-housed male and female rats. When core (NAcC) and shell (NAcS) were recorded simultaneously, there was greater ES DA release in NAcC of pair-housed females compared with single females and males. Housing did not affect ES NAc DA release in males. In contrast, there was significantly more ES DA release from the DLS of female rats than male rats. This was true prior to and after treatment with methamphetamine. Furthermore, in castrated (CAST) males and ovariectomized (OVX) females, there were no sex differences in ES DA release from the DLS, demonstrating the hormone dependence of this sex difference. However, in the DLS of both intact and gonadectomized rats, DA reuptake was slower in females than in males. Finally, DA release following ES of the medial forebrain bundle at 60Hz was studied over four weeks. ES DA release increased over time for both CAST males and OVX females, demonstrating sensitization. Using this novel 16-channel chronic FSCV electrode, we found sex differences in the effects of social housing in the NAcS, sex differences in DA release from intact rats in DLS, sex differences in DA reuptake in DLS of intake and gonadectomized rats, and we report sensitization of ES-induced DA release in DLS in vivo.

Sex differences in vulnerability to addiction.

This article reviews evidence for sex differences in vulnerability to addiction with an emphasis on the neural mechanisms underlying these differences. Sex differences in the way that the gonadal hormone, estradiol, interacts with the ascending telencephalic dopamine system results in sex differences in motivated behaviors, including drug-seeking. In rodents, repeated psychostimulant exposure enhances incentive sensitization to a greater extent in females than males. Estradiol increases females' motivation to attain psychostimulants and enhances the value of drug related cues, which ultimately increases their susceptibility towards spontaneous relapse. This, along with females' dampened ability to alter decisions regarding risky behaviors, enhances their vulnerability for escalation of drug use. In males, recent evidence suggests that estradiol may be protective against susceptibility towards drug-preference. Sex differences in the actions of estradiol are reviewed to provide a foundation for understanding how future research might enhance understanding of the mechanisms of sex differences in addiction-related behaviors, which are dependent on estradiol receptor (ER) subtype and the region of the brain they are acting in. A comprehensive review of the distribution of ERα, ERß, and GPER1 throughout the rodent brain are provided along with a discussion of the possible ways in which these patterns differentially regulate drug-taking between the sexes. The article concludes with a brief discussion of the actions of gonadal hormones on the circuitry of the stress system, including the hypothalamic pituitary adrenal axis and regulation of corticotropin-releasing factor. Sex differences in the stress system can also contribute to females' enhanced vulnerability towards addiction.