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Post 7 Sexual dimorphism in Rat Cocaine Responses

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Holly et al. 2012 and Vassoler et al. present an interesting look not only into the susceptibility to drug abuse and addiction but how sexual dimorphisms may alter this behavioral response to drug administration. Holly et al. 2012 closely examines how sex and differences in hormonal levels may affect the likelihood of rats to “binge” or are more likely to develop behavioral responses to prolonged drug use when faced with social defeat stress. Interestingly, social defeat stress along did cause a heightened effect in both sexes but had a much more profound effect on the dopaminergic response to cocaine in female rats. One shortcoming is the mechanism by which estrogens may affect this heightened sensitization. In the first assay, it is clear that female estrous cycle socially stressed rats have the higher behavioral response of walk duration when administered cocaine as compared to non-estrous. But, in the second and third experiments the estrous condition is collapsed to only show females with a higher NAc dopaminergic response and binge behavior, especially in the socially stressed condition. Interestingly, this represents more motivated drug seeking in which estrogens don’t seem to have an effect. To me, it would be highly interesting to parse this out as to why these different behaviors are more or less susceptible to estrogens. For example, it would be interesting to see if there is no effect of estrogens on DA dialysis when cocaine is administered. 
            
            Vassoler et al. 2013 shows the possible protective effect of chronic paternal cocaine use in reducing male offspring susceptibility to prolonged cocaine dependency. This study is very thorough and shows clearly that higher transcription and levels of BDNF in the mPFC in males is most likely responsible for this dimorphism in chronic drug response. But an interesting consideration arises when a deeper look is taken into why there is a larger response in males only. The genetic inheritance should be similar for both sexes (except for sex-linked genes). It would be interesting to see if somehow the early estradiol in brain development of males interacts with a known inherited gene changed by chronic cocaine use. This question could definitely be answered through means of sequencing sal vs coc sired groups. Overall, it is very interesting to see how there are generational protective mechanisms for males but possibly not female rats. In a larger scope, these sexual dimorphisms in drug response and addiction risk would always be interesting to view at a human translational level. 

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