Rats, Cocaine, and Sex Differences - John Lambert

            The papers this week seem to be less directly connected than most of the previous pairings. While Vassoler et al. (2012) explored paternal epigenetic inheritance, Holly et al. (2012) focused on sex differences in behavior as a result of stress. The main similarities between these papers was their use of cocaine, their use of rats (different types, I might add), and the examination of some sex differences. Each paper made for interesting reading. As I mentioned before, Vassoler et al. examined the effects of chronic cocaine exposure to male rats on their offspring. They did this by exposing male rats to unlimited cocaine (or saline) for 60 days, then allowing them to mate. The offspring (F1 generation) were then allowed to grow and tested for cocaine resistance, learning deficits, and changes in neurochemistry. Vassoler et al. found that cocsired males seemed to exhibit a resistance to cocaine, and possessed increased brain-derived neurotropic factor (Bdnf) proteins, mRNA, and promoters in the mPFC. Female offspring did not exhibit any significant difference in resistance to control. Association of acetylated histone AcH3 with Bdnf promoters was increased in the sperm of sires that self-administered cocaine. This indicates that adult male rat cocaine self-administration reprograms the germline, resulting in enhanced BDNF expression in the mPFC, which blunts the reinforcing efficacy of cocaine only in the male progeny. Holly et al. led three experiments, all following social defeat (stress). One examined acute cocaine’s effect on behavioral sensitization, the second examined its effect on neural sensitization. The third examined cocaine “binge” behavior. Experiment one found that estrous cycle had a negative effect on behavioral sensitization, while experiment two found that there was only a significant DA effect for stressed females. The last experiment clearly demonstrated the effects of stress, and further found that females administer longer than males. Overall, both studies produced some interesting data. I really would have liked to have seen more behavioral tests in Vassoler et al. Though the paper’s focus was on the epigenetic effects, clearly demonstrating or exploring how behavioral differences tie in would improve the paper. Additionally, it might be worth exploring multi-generational effects (though that would get very complicated and expensive very quickly). 

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