Holly et. al.

This paper by Holly et. al. explore sex differences in cross sensitization of an episodic social defeat paradigm and cocaine administration. This was measured in three ways: locomotor sensitization, DA levels in the Nucleus accumbens shell, and cocaine self-administration. I was fairly convinced by these findings, because the experimenters made sure to account for possible variability that would skew data such as habituation to injections, housing males in proximity to females to ensure regular estrous cycles, “resident” mice being housed together, and most importantly, the circulating ovarian stages (estrus vs met/diestrus). As for the episodic social defeat paradigm itself, I was slightly wary of the difference between an “aggressive” male mouse and a defensive mother female mouse, and their interactions with male and female experiment mice. The authors did note the difference in attack strategies of the two resident mice, and seemed to dismiss this as a huge factor, but I feel like these might be two different environments, and this could affect the type of stress induced on the mouse. I also wonder if it matters whether the mice are attacked by the same sex and I would be interested to see results of females being attacked by male mice and vice versa.

This paper did have some intriguing findings; particularly that drug induced behavioral sensitization was not only larger but also longer lasting in females, especially stressed females. I believe it would be interesting to perform this same experiment but with a different social behavioral stress paradigm or a regular chronic mild stress without emphasis on the social aspect, and compare the results between the two.

The interaction between change in DA in the NaC and stress also showed interesting results, with a significant effect of sex observed in stressed animals but not non-stressed animals. The percent change in females also stayed elevated for much longer than males, and I think the mechanism behind this elongated DA elevation is worthy of further research. This shows a difference between DA circuits in stressed females and males in response to cocaine, perhaps (as the paper suggests) as a result of estradiol regulating dopamine. Overall, this paper provided a good start at piecing apart the sex differences in sensitization as a result of cocaine taking, but it seems to be more of a launching pad for further investigation than a paper making any definitive statements.