Before I go into the papers, I just wanted to briefly comment on the general lack of research conducted on female animals. I have heard about these discrepancies in my classes, so I did a quick Google search and found a study published in 2010 examining the sex biases in biomedical research. To my surprise, the field of study that was most biased to using male-only studies was neuroscience, with male studies outnumbering female studies 5.5 to 1. With known sexual dimorphisms and different morbidities for diseases, I believe it is of the utmost importance that the scientific community lobbies to include more female animals in their research designs. The majority of current research is still done solely on male animals, with only 15% of studies examining both males and females. Women comprise 51% of the population, and if we want our research to eventually lead to therapeutics, we should use animal models that represent that half of the population as well. Amazingly, the NIH did not mandate the enrollment of women in human clinical trials until 1993, and there is no current mandate for research to include female animals. If anyone wants to see the article, here is the url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3008499/
The Holly et al paper perfectly exemplifies the importance of sex-specific analysis. I had actually never heard of the differences in behavior in female mice going through different phases of the estrus cycle (which probably points to the lack of research on females), so I thought it was really beneficial to read about that. It was also interesting to see that they housed male mice close to the female mice in order to ensure regular estrous cycles, I wondered if that had to do with the male hormones influencing the estrous cycle (I should probably learn more about this before conducting my own research…). I thought this paper’s methods were valid, and the result that stressed females were the most vulnerable to cocaine addiction was interesting, but otherwise I didn’t find the paper that captivating. I had trouble understanding the significance of increased locomotion in response to cocaine and how this would relate to increased susceptibility to relapse or addition. I also wished the authors had gone into more detail about the dopaminergic changes they found, and what kind of implications those could have on the addiction/reward pathway. This neural circuitry is also involved in OCD and anxiety, which are also more common in females. Perhaps changes due to stress induced anxiety could be mediating changes in this pathway that is then hijacked by cocaine.
The Vassoler et al paper was interesting because it shows the role that the father can have in downstream genetic effects on the offspring. The fact that the father can pass on epigenetic changes has so many implications for multiple diseases. While I was reading this, I wondered why the authors didn’t examine the acetylation of the male and female offspring sired by cocaine-experienced rats. I would have liked to see whether both male and female offspring had the epigenetic changes in their genome, to get a clearer idea of why females didn’t express the cocaine-resistant phenotype. If both sexes inherit the increased acetylation, then I could get on board with the author’s hypothesis that the differences in hormone and testosterone expression is what dictates expression of the protective phenotype. This paper has some great research with wide implications, but will be hard to translate into human experience. Like the authors mention, addiction has so many environmental factors as well, and currently it is thought that children from addict fathers have a higher risk of addiction. Maybe studies using children with absentee fathers could evaluate risk of addiction, accounting in socioeconomic conditions and behavior of the mother too of course. Addiction is such a variable disease, but it definitely helps to solve small pieces of the puzzle, and find the genetic and neural pathways that contribute to increased or decreased risk.