This week's papers address sex differences in both transgenic and environmental factors on cocaine usage. I found it interesting that while one paper found results consistent with human epidemiological studies, the other paper's results were counter intuitive.
Holly et al used episodic social defeat stress to explore the effects of stress on cocaine usage and sensitization. One issue that is addressed with the use of social defeat stress is that male and female aggressors attack in slightly different ways and therefore, the experimental animals may experience different levels of stress. The researchers claim that there were no differences in stress responses such as weight gain, corticosterone levels, and behavioral changes. However, this data was not shown and it appears to be anecdotal. An additional experiment that they could have included would be a social interaction test to see if the experimental rat did in fact learn to be afraid of the aggressor. In order to completely avoid the confound of sex differences in aggressive behavior, they could have also used chronic immobilization stress instead of episodic social defeat stress.
Vassoler et al took a transgenic approach to measuring the effects of cocaine resistance and sensitivity. They specifically focus on a pathway of increased BDNF in the mPFC which is at least partially a result of histone H3 acetylation. These transgenic changes cause male offspring, but not female offspring, to have resistance to cocaine addiction. However, because these rats are not part of a complex society, nor did they experience the environmental factors relevant to humans, the results were counter intuitive to what one may expect. In human epidemiology studies the offspring of cocaine users were actually more likely to become users themselves. I am curious to know if the increased BDNF levels found by Vassoler et al altered dopamine levels in the nucleus accumbens. Because dopamine is highly important for reward mechanisms, I wonder if the increased BDNF in the mPFC causes a decrease in dopamine that would cause cocaine to be less rewarding.