Holly et al. 2012

Holly et al. (2012) explored the effects of stress on behavioral and dopaminergic cross-sensitization to cocaine and cocaine binging based on gender. They not only utilized male and female differences, but also non-estrus and estrus females. The social defeat paradigm was used to induce stress in both genders, and then walking locomotion and dopamine levels in the nucleus accumbens were used to measure behavioral and dopamine sensitization respectively.  I found their experimental design very interesting, particularly in regards to the use of gender separation. Their choice to incorporate the estrous cycle was particularly relevant, as indicated by their results. I also appreciated that they performed the social defeat stress paradigm 10 days before the testing so as to show the long lasting effects. Regrettably, the sample size was small, as the researchers noted, so further studies should consider adding more rats to future investigations.

As depicted in their figures, there is a significant effect seen between genders in terms of locomotion after stress and cocaine exposure. Of particular interest to me throughout the study was the estrus female group. They demonstrated significant increases in locomotion in both stress and non-stressed groups and at both 5 and 25 minute intervals after cocaine exposure. The non-stressed increase, which was significantly higher from both males and non-estrus females, surprised me. This demonstrates how impactful the estrus cycle is in regards to neurobiological manipulation, especially given the significant comparison to non-estrus females. Additionally, the duration of the effects between genders was striking. The stressed male rats only had an increased locomotive response to cocaine at the 5 minute mark, and returned to baseline at the 25 minute mark. The stressed females both maintained high locomotion from baseline at the 25 minute mark.

Furthermore, the presentation of the dopamine changes depicted the magnitude and duration differences between stressed and non-stressed males and females. I was rather disappointed that they chose not to separate the females into estrus and non-estrus for this aspect of the experiment, especially given the previously demonstrated results in the behavioral test. The females are clearly more sensitive in comparison to the males. Interestingly, they noted that tonic DA levels are different for males and females even without circulating gonadal hormones. Holly et al. (2012) suggest estradiol as a possible modulator of DA that affects sensitization following social defeat given that it only affects females and not males. Examining DA reuptake mechanisms in the NAc in relation to the presence of estradiol could also be interesting.

After reading this, one possible future study could examine the relationship between stress, oral contraceptives, and drug sensitization. Given the amount of females that current take some kind of oral contraceptive, some of who may fall into a cohort of socially stressed recreational or addicted drug users, this research could be very pertinent. This study definitely warrants the use of females animal models, of varying estuation, in research, especially given that females are over half of the population.