Estrogen and Self Administration of Cocaine - Annissa DeSilva


In the articles this week Holly et al. and Vassoler et al. investigated how environmental exposure to stress and genetic predisposition may lead to enhanced susceptibility to cocaine addiction. Interestingly both studies separated the mice by sex to observe sex specific differences in cocaine addiction. Holly et al found that episodic stress exerted a larger effect on female mice versus male mice. Compared to the stressed male stressed mice the female mice had a greater locomotor response to cocaine and longer cocaine binges than males. What I found most interesting about this paper was the discussion of gonadal hormones, specifically estradiol’s implication in enhancing susceptibility to addiction. The researchers took vaginal smears before each task, however concluded that only duration walking after cocaine administration was affected by estrous cycle. Holly et al suggest that in terms of cocaine binging, effects may not have been seen due to the fact that the binge spanned the entire estrous cycle. The method of vaginal smearing seems too “general” in a sense to actually investigate the role of estrogen fluctuation in cocaine binging. A better experimental design would to repeat the episodic stress paradigm on ovariectomized  rats (OVX), where each experimental group is receiving progesterone and estrogen replacement at levels that mimic each four phases of the estrous cycle. This would allow for them to pin point at exactly what phases this increased sensitization happens, and if progesterone may have an effect since it is also elevated during the estrous cycle.
Vassoler et al found that offspring of cocaine dependent rats inherited a decreased acquisition for cocaine self-administration accompanied by increased levels of BDNF mRNA in the pre frontal cortex but this was not seen in female offspring. The paper briefly mentions circulating estrogen as a potential reason why no effects were seen because its an enhancer of cocaine effects it also mentions progesterone having the opposite effect. This was a little confusing because the highest levels of circulating estrogen are during the estrous cycle but simultaneously during this time there is a spike in progesterone. Either way it would be interesting to further explore if the resistant phenotype was affected by estrogen interactions again by seeing if the resistant phenotype is present in OVX, OVX+E, or OVX+P offspring. This could potentially provide further clarification if the inability to inherent the resistant phenotype is related to gonadal hormones or as the author also mentions, the sexually dimorphic features of the brain.

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