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Blog Post- Sex Differences in Drug Abuse Behavior

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The two papers were very interesting to read, especially as they both discuss sex differences in addiction (a very interesting topic in my opinion)  and show how findings can be across male and female rodents can vary. Holly et al, in 2012, presents a paradigm of social defeat stress and its relation to drug addiction. The experimental rats used in investigating social defeat stress model are same sex resident. However, I would be curious to know how opposite sex experimental rats would have an effect on the stress response. Would the response be even greater if a male rat was causing social defeat stress of a female rat? Although the paper represents a throughout approach towards addiction and sex differences, I would also like to learn more about how drug tolerance and withdrawal are affected in regards to both stress and addictive behavior.  
From previous neuroscience classes, I have constantly encountered the topic of hormones’ role in behavioral responses and how largely they differ between males and females. Therefore I would like to find out more about the estrous cycle and how estradiol and even testosterone actually play a role in stressful behavior and addictive responses. The researchers claim that there is an increase in female response during the estrous cycle compared to the non-estrous cycle, and that estradiol is seen to affect behavioral sensitization. Building off of that, throughout the paper I became curious in knoing what other components than hormones would have an effect on sex differences in males and females, which was clarified when they mentioned that D1, D2 and DAT distributions varied across sexes. Overall, I thought Holly et al did a good job in the approach of looking at addiction in cross sensitization through socially defeated rat models where the emphasis was on females, showing longer lasting stress and longer binge duration than that of males. 
Following the similar topic, Vassoler et al investigates cocaine self-administration in relation to genetic, environmental and epigenetic factors. The comprehensive findings suggest that paternal cocaine self administration results in a decline in cocaine self-administration in male offspring. One kind of methodology the researchers used was epigenetics. Epigenetics are beneficial as they may even strengthen present findings from early prenatal influences in offspring. An example of how it can be used to further investigate the effect of early life stress is seen in research by Bilbo and Schwartz in 2011. They used dogs as subjects and found that if they were exposed to a “good” upbringing/maternal care, then they had a long-live microglia early in life which affects their development later in life. As Vassoler looked at epigenetics and their effect on drug addiction, Bilbo and colleagues found that an increase in methylation presented a reduction in gene expression (in this case of increased maternal care). They therefore demonstrate that early life stress is a mechanism that can be passed on to a future generation. 
Although the Vassoler et al paper have both males and females as their cohort, they soon only generalize male findings to the larger extent. One aspect that was noticed throughout both papers was that they did not have a large cohort to start with, and even had to exclude more rats due to numerous faults in measurements. This therefore makes it questionable as to what extent the analysis is valid, and how a limited number of subjects contribute to validity of the findings. As a last impression- in the discussion of the later paper, they state that the bed nucleus (which is implicated in stress and addiction) is larger in males than in females- then how are Holly et al able to present findings that suggest that females are longer lasting in stress than males? Is it due to brain circuits rather than the size of the region? 

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