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Sex differences and drug abuse

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Holly et. Al (2012) used an episodic social defeat stress paradigm to understand the differences between male and female rats as well as the effect of the female estrous cycle in behavioral and dopaminergic cross-sensitization to cocaine. The results indicate that episodically stressed females have significantly greater behavioral sensitization than controls as well as stressed male counterparts. This behavioral sensitization of increased locomotion activity in response to cocaine was also longer-lasting in the females, with higher levels seen in estrous females. There were no obvious group differences in neural sensitization, but the authors noted this limitation may be due to small sample size, and that more subjects might show statistically significant numbers. I’d be curious to see a follow-up study specifically built around the idea of stress exposure and circulating estradiol on dopaminergic function in females. In terms of its clinical usage and applications, I thought about how it’s known that women are more susceptible to craving and relapse, and if this has anything to do with estradiol/dopaminergic interactions. For example, if we compare this to the female menstrual cycle, is an adult female more likely to fall into a pattern of relapse after trying cocaine during a specific time of the cycle and furthermore, would she crave it more during a certain period of the cycle? Understanding this and the interaction it has could potentially see a future in developing more efficient treatment plans for substance use disorders.

Vassoler et al. (2013) presented robust epigenetic data illustrating how paternal cocaine self-administration causes an acetylation effect which literally reprograms the germline to inherit a neural and behavioral phenotype of reduced cocaine reinforcement. I thought this paper was really interesting, and especially enjoyed the data regarding a potential functional change in sperm that may be caused by cocaine. Similar to my comments regarding the Holly et al. paper, I’m intrigued by substance abuse studies on both a sex difference level and a developmental level (i.e. adolescent substance abuse problems and implementing treatments so patients don’t find themselves in patterns of relapse). We have ways to go in terms of understanding addiction and why it happens, but I’m excited to see how studies such as these might manifest into clinical applications for humans. Furthermore, I appreciate how female cohorts--which have been wrongfully neglected in the world of neuroscience--were heavily included (and the stars of the show in Holly et al.) in both these studies. 

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