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Sex Differences In Drug Abuse Behaviors

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Holly et al’s paper focuses on sex differences in stress and the effects of cocaine on each stressed vs non-stressed male and female rats. Ultimately, it was determined that female stressed mice are more prone to cocaine use than stressed males. Additionally, estrous cycle did not have an effect other than increased walking (a measure of stress) after the social defeat paradigm and cocaine administration in females in estrus. There was also a general trend towards females having more dopaminergic tone. First, I want to address the stress paradigm, a social defeat model using the same sex as the perpentrator. For males, it was a larger dominant male, and for females it was a lactating dame. The study tried to keep the stressful experience as close as possible for males and females, monitoring corticosterone hormone levels, weight gain, and behavior. They observed no drastic differences. I thought that this was clever and indicated that the experiences were somewhat the same in terms of stress level, however, there are potential intrinsic differences in how different sexes experience a stressful event. It is possible one rat was more prone to be affected by this event than another, similar to how some individuals are more prone to PTSD. I am not sure how to equate stress levels in rats, but I think this paper did the best that they could. I also questioned the walk duration they used as a measure of anxiety/stress. I am personally not familiar with the measurement, but it makes sense that a stressed animal may have more locomotor agitation when stressed and given amphetamines. It also made me think of the darting behavior we discussed last week. Is it possible that the darting behavior and walking may be related? Could they be some form of escape behavior? Lastly, I remember learning in Biopsych that neurologically, males handle acute stress better than females, and females handle chronic stress better than males. I would have liked to have seen the neural connections of the male and female rats and if they had lost any dendrites. I would have also been interested in seeing the effects of a longer term stress paradigm and if the male rats would have binged more than females if the social defeat paradigm persisted. Overall, I thought Holly et al did a great job pointing out that there are sex differences in stress and researchers need to be studying both males and females for a whole picture. This can lead to more insights in not only how the two different sexes handle stress and anxiety, but also addiction. 
Furthering the discussing of sex differences, Vassoler et al performed an interesting study examining a cocaine resistant phenotype that only presented in males. Specifically, these males were sired by other males that were receiving cocaine, and when studied, they did not self-induce cocaine administration compared to controls or females. The researchers observed increased BDNF proteins in the mPFC. Interestingly, when the BDNF receptor was blocked with an antagonist, the self administration was increased again. I think this article is extremely interesting and complements Holly et al in its continuation of sex differences. Once again, sex differences needs to be studied to understand the whole picture. The researchers hypothesized that the reason the cocaine resistance effect was observed only in male offspring and not females had something to do with testosterone. I am also curious about the role of the dopamine receptors as the previous article mentioned there were differences between males and females. Additionally, this paper suggests spermatozoa and epigenetics play a much larger role in genetics than previously thought. It also has major implications for addiction and sexual dimorphisms in both disease mechanisms and treatment. 
Overall, I thought that both of these articles highlighted important points as to while both sexes need to be studied in rats. The first study indicated that female rats react to stress differently, and the second indicated that males may potentially have a cocaine resistant phenotype. Both have important implications for psychiatric illnesses and addiction. I would like to see further repetition with a larger cohort for rat studies using both sexes.

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