Holly et al. (2012)

I found it interesting that Holly et al. (2012) took into account so many factors that could effect sensitization and increase cocaine use after a social defeat stress paradigm.  Their independent variables were sex, stress, and estrus cycle.  Social defeat had a more significant behavioral and neurochemical effect in females than in males.

It was interesting that they found no difference in accumbal dopamine between groups, especially since there is such a big difference in striatal dopamine between males and females.  Male rats have higher extracellular striatal dopamine than females even when both sexes are castrated.  This means that there are probably neural factors that affect dopamine release, reuptake, or firing frequency in female rat brains.  What makes it more confusing is that estradiol increased dopamine tone in females but had no effect on castrated males.  This might be due to sex differences in the number of estradiol receptors present in the striatum.  It would be interesting for the researchers to measure the extracellular dopamine of stressed castrated females just to explore the interactions between estradiol and stress. 

           Holly et al. (2012) also found that cocaine increased the percent change in baseline accumbal dopamine levels between stressed and non-stressed males.  Cocaine did not have this effect in females.  However, stress caused extracellular dopamine levels to stay elevated much longer in females than in males.  The authors mentioned that this is probably due to an inability to clear the NAc synapse, but I think that looking at sex differences of upstream firing in the ventral tegmental area (VTA) would be good to do as well.  Overall, Holly et al. (2012) did a good job of explaining sex differences.  This type of experiment is normally hard to follow due to the different factors present, but I think that the authors did a relatively good job of keeping everything organized.