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Sex Differences in Drug Abuse

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March 30 Papers (Holly et. al, Vassoler et. al)

Holly et. al’s 2012 paper explores the sex differences in neural and behavioral cross-sensitization to cocaine following social defeat stress in rats. The study found that while both sexes develop this cross-sensitization, the effect is larger and lasts longer in females, possibly due to estrogens and their role in modulating mesocorticolimbic dopaminergic function. Additionally, female rats consumed more cocaine than male rats after undergoing the social defeat stress paradigm. 

These findings could have great clinical relevance in developing treatments for drug addiction in humans, particularly for women who have a heightened vulnerability to cocaine addiction, use the drug more often than men, and are more likely to relapse. Perhaps the development of treatments for drug addiction in men and women should be carried out separately if it isn’t already, and should focus on mesocorticolimbic dopaminergic function, with special consideration to how it is affected by estrogen in women. Moreover, children often inherit a susceptibility to drug addiction from their parents, and it would be interesting to know whether women are more likely to inherit this susceptibility from their parents than men, or inherit it to a larger degree. Taking it one step beyond stress, I’d be curious to read research regarding the neural or biological mechanisms behind how stress-related disorders such as anxiety or PTSD and increase vulnerability to drug addiction.

On the other hand, Vassoler et. al’s 2013 paper examines the epigenetic inheritance of a cocaine-resistance phenotype in the offspring of male rats that had been allowed to self-administer cocaine during spermatogenesis. The results of this study showed delayed acquisition and decreased intake of cocaine in the male, but not female, offspring of these rats. Furthermore, Vassoler et. al found that there was an increase in Brain Derived Neurotrophic Factor (BDNF) mRNA and BDNF protein in the medial prefrontal cortex (mPFC) of the cocaine-resistant male offspring, as well as an increase in association of acetylated histone H3 with BDNF promoters. The paper claimed that this might be at least partially responsible for the expression of the cocaine-resistance phenotype. 

I find the idea that what could be described as “life experiences” such as using drugs or undergoing famine can alter the genetics of offspring even just one or two generations down the line to be fascinating. What stands out the most about the conclusions drawn by this paper is that the inherited resistance to cocaine seen in the rats in this experiment directly contradicts what research has shown regarding how, in humans, the children of heavy drug users are often born with a susceptibility to drug addiction. It would be interesting to learn more about what underlies this difference between rats and humans in the genetic inheritance of drug-related susceptibility. Although I do not know how plausible this would be, these results make me wonder whether increasing association between BDNF promoters and acetylated histones and increasing BDNF mRNA and protein in the mPFC of humans addicted to cocaine, or their children, could potentially be an avenue of treatment for drug addiction. Finally, even though the paper gave valid reasons as to why only the offspring of male cocaine-using rats were studied in this experiment, it would be great if researchers could find a way to test whether the results of this study would be replicated in the offspring of female cocaine-using rats, especially given that as previously stated, women are more vulnerable to cocaine addiction. 

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