Sex Differences and Social Support Effects on Methamphetamine Self-Administration and Stimulated Dopamine Release in Nucleus Accumbens

Abstract

There are known sex differences in methamphetamine (METH) self-administration in rats. Recent studies have investigated social support and its attenuating effects in self-administration. More specifically, females that are socially housed self-administer less METH than single housed females, but social housing does not have an effect on males’ self-administration. I investigated social housing effects on METH self-administration when both cage-mates are self- administering METH. As in previous studies, I found that socially housed females self- administered less METH than single housed females and I found no effect of social housing in males. However, when looking at the individual differences, only on the first session of intermittent access did single housed females have more individuals in the HIGH active pokes during both drug-available and non-drug available. The individual differences diminished after session 1, suggesting that the attenuation of social housing in METH self-administration may not be beneficial long-term when both rats are going through self-administration. I also looked at how dominance played a role in motivation for METH and found that dominance decreased males’ motivation for METH, but no effects of dominance were found in females. Then, I investigated the effects of social behavior 24 hours after only one rat of the pair was injected with METH through an intraperitoneal injection (IP) (1.5mg/kg). I found that social play was not affected by treatment, however males spent more time doing social play compared to females. Thus, it is possible social play after METH exposure may be a negative experience for the males and shows why social housing is not beneficial for males but is beneficial for the females. Finally, I investigated the effects social housing conditions and sex on electrically-stimulated dopamine release (ES DA) after an IP injection of METH using a technique called fast-scan cyclic voltammetry. Previous studies have shown enhancement of DA release to ES with repeated stimulation over time, a process known as sensitization. I found that in both socially housed and single housed males, there was no sensitization of DA release in the nucleus accumbens core (NAcC) or nucleus accumbens shell (NAcSh). However, there was sensitization of dopamine release in the single housed females in the NAcC and NAcSh, but there was no sensitization in socially housed females. Putting these results together, these findings suggest that single housed females are more vulnerable to the addictive-like effects of METH because the DA responses in both the NAcC and NAcSh becomes sensitized to METH. In contrast, social housing in females is protective against sensitization of the DA response and the addictive properties of METH. For males social housing does not mitigate against vulnerability to METH self-administration even though ES DA release does not sensitize, perhaps because the instability of the social housing conditions makes the socially housed males as vulnerable as the individually housed males.