Sex Dependent Regional Differences in Dopamine Release Determined by Chronic Fast-Scan Cyclic Voltammetry in Nucleus Accumbens and Dorsal Striatum

Abstract

AbstractDopamine (DA) signaling in the nucleus accumbens (NAc) and dorsolateral striatum (DLS) is thought to contribute to sex differences in motivated behaviors. Using a chronic 16-channel carbon fiber electrode, electrical stimulation (ES) induced DA release in freely behaving male and female rats was recorded using fast-scan cyclic voltammetry (FSCV). In the NAc of gonad-intact rats, individually or pair housed, DA release was recorded simultaneously in the core (NAcC) and shell (NAcS) following 60Hz ES of the ventral tegmental area DA cell bodies. Electrode placement was determined post-mortem. No differences were found in stimulated DA release when NAcC and NAcS were recorded simultaneously in either males or females. In females, however, there was greater ES DA release in NAcS of pair-housed females than individually housed females. There was no effect of housing on ES NAc DA release in males. In the DLS of castrated (CAST) male and ovariectomized (OVX) females, DA release following ES of the medial forebrain bundle at 60Hz was studied over four weeks. There were no sex differences in ES DA release of gonadectomized rats. However, ES DA release increased over time for both CAST males and OVX females. In both sexes, reuptake decreased with the number of pulses, but females had slower reuptake at lower stimulation parameters. Using this novel 16-channel chronic FSCV electrode we reliably record stimulated DA release over time. Furthermore, we found sex differences in the effects of social housing in the NAcS and we report sensitization of ES-induced DA release in DLS.Significance StatementA novel electrode was used to record stimulated dopamine release over weeks in the nucleus accumbens and dorsolateral striatum of male and female rats. We find that pair housing, compared with individual housing, enhanced stimulated dopamine release in the nucleus accumbens shell, in females, but not males. These findings are important as they demonstrate that housing conditions can differentially affect neurotransmitter responsiveness to stimulation in a location and sex-dependent way. There were no sex-related differences in the dorsolateral striatum of gonadectomized rats. Importantly there was sensitization of electrical stimulation-induced dopamine release in dorsolateral striatum over four weeks. This indicates for the first time that sensitization of stimulated dopamine release can be demonstratedin vivoin dorsolateral striatum.