Holly et al. adopted a very clear and systematic approach to investigate the role of sex and estrous cycle differences in behavioral and neural sensitization to cocaine. Although they have been successful in outlining the role of sex differences in these behaviors, the role of estrous cycle differences has been under studied. They were only able to show estrous cycle differences in Experiment 1, but not in Experiment 2 & 3, and their explanation due to fluctuations of ovarian hormones across the binge was not convincing as this limitation could have been foreseen. Additionally, although they do highlight the role of estradiol in enhancing behavioral and neural sensitization, they failed to offer an explanation as to why this effect was seen. In other words, what might estradiol be doing that’s causing this heightened behavioral and neural response? What interaction does stress and estradiol have?
As for the Vassoler et al. paper, it was interesting to see a paternal transmission effect. One would assume that coc-spired offspring would display an enhanced sensitization to cocaine considering how there are various studies that show addiction might be genetically linked, thus it was interesting to see a cocaine – resistance phenotype. Since BDNF serves a protective function, it is not surprising that coc-sired male offspring had increased BDNF mRNA expression but what particular significance does exon IV have? I wish they had addressed that or provided more information on the role of exon IV. The paternal expression route becomes clear when the result of increased sperm Bdnf promoters is introduced, but I was still pretty confused as to what kind of association they were trying to propose. Are some acetylated histones retained and passed down to the male progeny?