Addiction to methamphetamine (METH) is a major public health concern, however there are no effective treatments. Although METH is used by both men and women, women are younger when they start using METH, and show higher rates of dependence compare to men. Women also report a higher exposure to traumatic events and often start using to cope with psychological problems. Social support has a positive influence on stress-coping and might also have protective effects against addiction and help promote decreased motivation to take METH. Females show greater motivation for cocaine than male rats and social housing (pair housing) attenuates the motivation for cocaine in females but not males. Here we investigate whether oxytocin (OT) mediates the effects of social housing on motivation for METH. It is hypothesized that the effects of social housing are mediated by OT-dependent attenuation of dopamine (DA) release in the nucleus accumbens core (NAcC) after drug taking is established and that these effects will be greater in females than in males. Previous research has established that social housing attenuates the METH-induced increase in DA in dialysate from the NAc, and chronic low dose OT attenuates the motivation for METH in female rats. The long- term goal of this project is to understand how social housing influences the rewarding effects of METH in males and females, the role of OT in this regard, and whether chronic intranasal OT may be a therapeutic agent for treatment of psychostimulant abuse in females and/or males. We will also investigate DA responses in the nucleus accumbens fast-scan cyclic voltammetry (FSCV) in isolated and socially-housed male and female rats. The results of these studies will provide an indication of the role of DA in the nucleus accumbens to mediate the effects of social housing and OT on motivation for METH. We will also explore whether chronic intranasal OT can be used as a therapeutic agent for the treatment of METH-addiction.
/relevance There are no effective treatments for methamphetamine addiction. The research proposed is important for understanding sex differences in the effects of a positive social environment on motivation for methamphetamine self-administration in male and female rats. The mechanisms mediating the protective properties of social support, and the role of oxytocin in this regard, may ultimately lead to improved treatment and prevention options for methamphetamine addiction in both women and men.
