Week 8 Article

The Holly paper exemplified the weight that gender holds in modeling neural mechanisms with animal models.  Their study was conducted using male rats and both estrous and non-estrous females, to observe the behavioral and neural effects associated with social defeat and cocaine taking.  Social defeat was administered four times over a ten-day span by an aggressor rat of the same sex, and after an additional ten days three experiments were done.  The first experiment tested locomotor activity and found that all males and females had greater activity after cocaine administration in the stressed group compared to the control.  Both the estrous and non-estrous female groups however showed overall longer walking duration then the males that additionally sustained for an extended time period.  Estrous females specifically had the most exaggerated results and differentiation baseline levels in the control group compared to the other gender cohorts.  This reflects strongly on the difficulties with animal modeling particularly regarding the prohibiting effects of the reproductive  cycle on females.  The in vivo micro dialysis in the second experiment showed elevated dopamine levels in the NAc of stressed mice across both genders, and graphically portrayed the more reactive and sustained response to DA administration in females specifically.  The elimination of the true control group was a little unsettling but the neural cross-sensitization was still conveyed.  The third experiment topped off the study with an interesting take on how different sexes vary in self administration tendencies of cocaine.  The females again had significantly higher levels of infusions and durations of binging than the males.  The stressed and non-stressed males would administer cocaine at similar rates but stressed males would binge for significantly longer than their controls. 

All these experiments paint a smooth picture of sensitization to dopamine administration after stress and how drastically sex can skew results while running the same tests.  The paper boils this down some more by splitting the female rats into estrous and non-estrous cohorts, and I’d agree that this is where more research needs to be focused.  I think a deeper look into the unique responses females can exhibit will expose more links between critical developmental periods and the manifestation of mental disease.