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Holly and Vassoler

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I was very excited to read these two papers because they closely relate to my final paper topic – sex differences of addiction and how prenatal conditions affect offspring susceptibility to addiction. The first paper, Holly et al, (2012) explores cross-sensitization to cocaine in rodents that have undergone the social defeat stress paradigm. The paper analyzes the sex differences in behavior and neurobiology, particularly comparing NaC DA levels, in addition to exploring the effect of the estrous cycle. I enjoyed this paper because the interplay of addiction and stress was not something I was going to particularly focus on in my paper, but after reading this study and doing some further research, I realize that stress is indeed a very important factor to discuss. I liked this model for the social defeat stress paradigm and how they modified it to include an aggressor of equal magnitude in females compared to males. I believe the concept of using lactating dams as female aggressors was discussed in class a few weeks ago so it was interesting to see this in action. Although a lactating dam seems the most comparable to a male aggressor, and the males and females did not differ in stress response, I still wonder if the qualitative differences between the methods have any affect on the stressed rodent. The results of the study show that stressed females, especially those in estrous, experienced the highest sensitization to cocaine (increased locomotion and higher levels of dopamine). They also report that the females’ response to stress lasted longer than the males. I find these results fascinating but still am left wondering what the major cause of this difference is, although this is perhaps due to my own lack of knowledge on the difference between male and female brains.  It is discussed that dopamine, hormone levels, and differences in structure all play a part in the sex differences discussed above but I would still be interested in learning more about the degree to which they each affect the addicted rodent. I would also like to see how different drugs, such as morphine or antidepressants, compare in terms of these categories. The results on stressed females in estrous were especially interesting to me 1) since it is often not studied and 2) since they were so much larger for this population. I would like to do more research on how estradiol and progesterone affect stress response and dopamine functioning to possibly include in my paper. Knowing this type of information would not just be beneficial for the research community, but could affect how females vs males are tested and treated for disorders such as addiction. 

The second paper by Vassoler, et al. (2012) also explores the sex differences in cocaine addiction by testing if it was possible to create a cocaine-resistant phenotype using epigenetics. This study also relates to my final paper as I plan to discuss how pre and post natal conditions affect addiction susceptibility in the offspring. The authors particularly looked at the levels and effect of BDNF in the mPFC, as it is known that increased BNDF in this area blocks behavioral effects of cocaine. The results of the study showed reduced cocaine self-administration in male cocaine sired rats. I thought this result was very interesting because, although the data makes sense, it goes against society’s overall understanding that addiction is heritable. There is definitely a lot we don’t know about addiction and its heritability, and I would like to read more about the genetic (and environmental) factors that are known to contribute. In terms of expanding this study, I would like to know more about the bed nucleus of the stria terminalis (briefly mentioned regarding its larger size in males) and if it shows any significant sex differences during this study. Additionally, I would be interested in seeing how females in estrous compare to the other groups, just as in the first paper, since it is known that estrogen enhances the effects of cocaine. 

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