First of all, I find it absolutely mind-boggling that the scientific standard up until recent decades has been to completely neglect sex differences in research. Nearly every sex difference-inclusive study I have ever read has yielded fascinating results about the modulatory role of circulating ovarian hormones, and as exemplified by the Holly paper, sometimes important findings arise such as the identification of estradiol as a facilitator of dopaminergic sensitization. The potential avenues of largely untapped research are boundless, and our understanding of the brain is lacking this dynamic.
I admired the experimental design in the Holly paper and thought the researchers did a good job highlighting the cross-sensitization/comorbidity effects in the female rats. Tangentially, I found it interesting that in one of the papers they cited, a group of male rats were treated with estradiol and their DA tone was observed – neither intact nor castrated males were affected by the circulating estradiol, but estradiol administration significantly affects DA tone in females. For some reason, I can’t wrap my head around why – females likely express more receptors for estrogen-like ligands in the brain, but since estradiol/estrogen can act as a transcription factor, I would expect it to at least have some effect in the male brain as well. I hope for more research on neurobiological questions such as these in the future.
The Vassoler paper is a promising model of heritable drug addiction risk factors, and the paper was wonderfully clear. The research lays out major groundwork for future studies on epigenetics (and sex differences!) in addiction and their discovery of the actual pathway for increased expression of BDNF in male CocSired mice is important, and honestly an impressive testament to the scientific method.