Cocaine addicted rats: Stress vs epigenetics

Even as society learns to accept people with physical disabilities and other mental illnesses, drug addicts and their addiction are still too often stigmatized and trivialized. This is especially pertinent to women, who, at all stages of addiction, display more severe behaviors compared to men. To examine this gender difference, experimenters turn to rats.
Holly et al. (2012) sought to find sex differences in behavioral and neural cross-sensitization, and cocaine binging behavior, as a result of episodic social defeat stress. It was interesting to see their implementation of a social defeat paradigm on female rats since  studies that study only male aggression (like the ones we’ve seen in past papers) lacked generalizability. In previous class discussions, the possibility of taking advantage of innate maternal drives to model female aggression. So, I thought it was a pleasant surprise to see this current study use lactating dams as the “resident” in the paradigm. The researchers also predicted a greater effect in female rats in ovulating phases of the estrous cycle because of critical hormone surges. This prediction was not supported by their data. Their conclusions, calling for more research to be done on ovariectomized (OVX) rats to find support for estrogen modulating the relationship between stress exposure and estradiol, were also little unsatisfying, especially relating to their second experiment.
Vassoler et al. (2013) found striking evidence for a cocaine-resistance effect in male cocaine-sired rats. The researchers investigated the integral cocaine-resistant role of BDNF in the mPFC, using ANA-12, an antagonist to the receptors through which BDNF signals, thereby effectively “silencing” the protein. Interestingly, this resulted in increased lever presses for the ANA-12 group compared to the cocsired group, suggesting that BDNF expression was indeed responsible for the effects seen in the paper. Given that BDNF supports neuron growth and that the PFC is associated with executive function and working memory, further addressing questions probing this relationship would be an interesting next step. Additionally, my other questions involve looking at the reward system in the VTA to ask if similar protein patterns emerge and if these F1 cocsired rats experience less “pleasure” from cocaine.

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