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Post 8: Sex Differences in Drug Addiction

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Increasing our understanding of susceptibility to drug addiction disorders is critical for preventing and reducing risk of developing such disorders. Holly et al. (2012) and Vassoler et al. (2013) both consider the effects of sex on susceptibility to increased cocaine use as well as the impacts of stress and paternal experience with cocaine, respectively. While these studies both address important concerns in regard to susceptibility to stimulant addiction, they leave many questions unanswered and introduce additional questions. 

One question I had while reading these papers, especially Holly et al., was what aspects of sex differences between male and female rats might have led to the behavioral and neurochemical differences seen in response to cocaine exposure. Because females in estrus/proestrus had more robust differences from males in locomotion, it would seem that sex hormones are involved, but I am interested in the extent to which they impact cocaine sensitization. It would be interesting to run the same experiment on ovariectomized females and castrated males, as well as ovariectomized females receiving testosterone and castrated males recieving estrogen, to determine if neurological or developmental factors are also responsible for the administration of cocaine, behavioral, and dopaminergic sex differences seen in response to cocaine. These results may also be telling for the impact that hormone therapy for transgender individuals may have on susceptibility to drug addiction, especially as these individuals may already be at higher risk due to the stress associated with gender dysphoria and transitioning. 

Vassoler et al. also left me wondering what specifically led to the differences that were seen between male and female CocSired rats, causing effects sire cocaine experience in males but not females. I speculated whether there may be a genetic sex difference, such as a Y-chromosome gene that may add to or influence the differential effects of BDNF that were observed in male CocSired rats. I also considered whether the cocaine itself or the behavior of seeking cocaine drives the epigenetic changes that lead to differential self-administration of cocaine in male offspring. Perhaps the neurological changes conferred by the cocaine itself lead to epigenetic changes, or maybe the epigenetic changes are a result of changes in reward-seeking circuits. It would be interesting to test this by administering cocaine to sires non-voluntarily (testing whether the cocaine itself causes changes) and allowing for voluntary self-administration of sucrose (testing whether any reward-seeking behaviors cause changes). Doing so could contribute to knowledge of both epigenetics and factors that drive susceptibility and resistance to drug addiction. 


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