Vassoler et. Al

Epigenetics is something that has always fascinated me, and this paper brings to light the fact that, even in rats, your parents’ decisions before you are even conceived may have a lasting impact on who you are. Vassoler et. Al. created a heritable phenotype of cocaine administration in paternal rats, and then observed the effects of this phenotype on the offspring. I liked the approach to this paper because unlike other papers that focus on the animal with deficits, they instead looked at the animal that demonstrated a resilient phenotype, (one not submissive to the paternal cocaine administration). They then looked at what was different about the cocaine-experienced males, in hopes of understanding what allowed the animal to avoid developing the phenotype of cocaine administration. This study found that cocaine experienced male offspring somehow avoided the inheritance of cocaine administration from the sire, and this could be a result of increased BDNF protein in the mPFC as well as increased association of acetylated histone H3 with Bdnf exon IV. The portion of the study that convinced me of the role of Bdnf in the resilience of the males was when they administered ANA-12. Bdnf signals through TrkB receptors, and ANA-12 is a TrkB antagonist. Administering this antagonist reversed the effect of cocsired rats, demonstrating fairly convincingly Bdnf expression in mPFC reduced cocaine reinforcement in males. Their arguments were also made stronger by using two different requirements for cocaine administration (PR, FR1), as well as including the female cocsired data to contrast the male results.

While all this data is convincing, the paper did make a valid point in the discussion that human genetic studies, including the results from this paper, are correlational. While studying using animal models to imitate genetic scenarios is effective, I think at this point in science, it is impossible to find data that can completely account for the environmental contribution to these studied mental disorders in humans. That being said, I appreciate that they accounted for the sire influence on maternal behavior. I think it would be interesting to conduct further studies on this aspect not just in drug addiction, but other disorders as well. Because of the variability of the type of mother the sire is mating, I believe it is hard to make any findings from this study definitively translatable to humans. Despite this, Vassoler et. Al. made notable advances the paternal role in epigenetics of drug addiction. I would also like to see a longitudinal study testing the F2 generation to observe if this phenotype of cocaine administration can be passed through multiple generations.