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Examining the Sex Differences in Cocaine Addiction in Rats

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Both of these papers aimed to examine the sexual dimorphisms that contribute to cocaine addiction susceptibility, either through the lens of social defeat stress or paternal cocaine use. The first paper, published by Holly et al. in 2012, not only examined the differences between male and female rats, but also addressed the variation within the female group as a result of the estrous cycle. One aspect of this paper that I found particularly interesting was the difference in increase in dopamine in the NAc from baseline across the male and female groups. The data showed that while there was a greater increase in local dopamine in the stressed groups of both sexes, the dopamine levels returned to baseline within 60 minutes in the male group, but stayed elevated for much longer in the female (35-45 minutes longer than in the males). I found this data very compelling, but it did lead me to wonder what developmental steps are at play that would make female rats more susceptible to this prolonged dopamine increase. Do sexual dimorphisms cause this prolonged dopamine release, or does the heightened dopamine response to cocaine cause circuit changes or plasticity that feeds back to perpetuate a more robust addiction pathway? 

The second paper, by Vassoler et al., examined the epigenetic inheritance of a cocaine-resistant phenotype, particularly in male rats with paternal cocaine exposure (“cocaine-sired males”). The data from this paper suggests that increased BDNF in the mPFC of cocaine-sired males contributes to a cocaine-resistant phenotype, which was not seen in the female rats. This led me to wonder what other factors contribute to the lack of resistance in the female rats, and it would have been interesting to see the methods from the first paper employed in this study. Firstly, I think it would have been interesting to see if there were differences in estrus cocaine-sired females versus met/diestrus cocaine-sired females, because it makes sense to me, based on the first paper, that estrus females would be more susceptible than diestrus females. Also, conducting a similar dialysis experiment to examine the levels of dopamine in the cocaine-sired females could be an exciting direction to take (as heightened levels would explain the higher cocaine self-administration in female rats). Overall, I found both of these papers interesting and highly relevant to a wholistic understanding of the neural mechanisms that underly cocaine addiction. 



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