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Factors in Drug Abuse in Rodent Models

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Holly et al. 2012 studied the sex differences in rats associated with cocaine usage in repeated social defeat stress episodes. This paper was particularly interesting to me as it took major variables that affect human functioning into account. First off, as we have discussed in class, looking at sex differences in animal model research is very important for later clinical applications. Women are the majority of diagnosed cases of disorders such as mood disorders and PTSD and therefore more attention to research should be done in both sexes. Secondly, Holly et al. look at the effect of stress on the usage of cocaine. They drew this directly from human clinical data and this research could propagate a deeper understanding of the relationship between stressed individuals and drug usage. Lastly, a part I found quite engaging with this paper was their use of a 3 pronged approach to studying the effects of cocaine on stressed and unstressed rats. They used behavioral sensitization, in vivo microdialysis and cocaine self administration or a “binge” test. I found their approach quite all encompassing as they were able to look at behavioral phenotypes resulting from the combination of sex, stress and cocaine, the hormonal changes of DA in the Nucelus Accumbens providing information on the reward system associated with cocaine and they looked at the behavioral phenotype of addiction using the binge test. I appreciated their attempt at providing a well rounded analysis of the effects of stress and cocaine usage on male and female rats. Another element that pleasantly surprised me about this paper was their usage of a repeat social defeat paradigm for both male and female mice. At first I was quite skeptical as to whether they would be able to pull it off considering the lengthy discussion we had in class about the transferability of the social defeat stress paradigm from males to females, however they brilliantly made use of lactating dams to introduce aggressive behavior to the females. Although the closeness of the paradigms between the male and female paradigm could be questioned, and the authors did point this out themselves, I believe it was a great attempt at bridging the gap between paradigms being used for both male and female testing. A future direction I would like to see is evaluating the cause for changes in DA levels in the NAc. The authors had a few hypotheses for this such as increased DA neuron firing, increased DA receptors or modified reuptake mechanisms for DA. This particular mechanism was very interesting to me and I would like to know more about it as the major concern with cocaine addiction, as I learned in my psychopharmacology class, is that there is a change in regulation of the receptors that cocaine is a ligand for. Therefore I am curious as to the mechanism of modified DA regulation and whether they are the same. 

Vassoler et al. 2013, took quite a different approach to studying the effects of cocaine on rats and the nature of their research presented an apparent difference in sex response to cocaine. I was personally intrigued by this paper as I have done research on transgenerational immunity in Manduca sexta, the tobacco hornworm, and a lot of the methodology done by Vassoler et al. are very similar to what we did to study the effects of maternal and paternal stress on the viability and immune function of offspring. The major finding in the paper that cocaine or paternal exposure can cause functional changes in the sperm provided to the offspring. These epigenetic changes in response to parental exposure to environmental factors is the same hypothesis suggested by my lab and their results show that acetylation of DNA in response to cocaine exposed fathers seems to lead to an increase in BDNF in the offspring, further leading to increased drug resistance. In my lab we look at maternal and paternal exposure to bacterial stress to observe for changes in regulation of miRNA or methylation/acetylation changes in reproductive tracts of the males and females as well as offspring viability in response to exposure to the bacteria. I enjoyed the major overlap between the work done by Vassoler et al. and the work I have contributed to in my lab. Another section of the paper I enjoyed was the observation to control for in utero cocaine exposure and potential influence of previous cocaine experience by dams on maternal behavior. This seemed to me a good control for the very quickly fluctuating hormonal levels during pregnancy as well as postpartum experience of the offspring. 

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