Holly et al (last week) and Vassoler et al.

In the Holly et al paper, the research focused on the role of stress and sex differences in sensitization to cocaine, and the effects of sex differences on self-administration of cocaine. To test these differences, they focused on both male and female rats, and even separated the females based on their estrous cycles. To test the effects of cocaine on stressed versus unstressed rats, they had the rats perform an open field test to test locomotion. The stressed rats showed significantly more locomotion than the unstressed rats, and the females showed significantly more locomotion than the males. It was interesting that females were significantly more effected by the cocaine than the male group, indicating that sex may play a large role in the effects of drugs. This paper also looked at the differences in dopamine levels following cocaine administration in the groups of rats. Females had significantly higher dopamine levels following administration, which could account for the differences in locomotion and general greater effect seen in females. It was also fascinating to me that social defeat stress obviously had a much larger effect on females than on male rats, which seems to parallel the effects of stress on human beings.

These results were particularly of interest because they could have drastic implications for future research. Perhaps more research will be conducted using female animal models to observe the obvious yet vastly undiscovered differences between sexes in response to drugs, as this is a very applicable body of research to human subjects.

In the Vassoler et al paper, it was interesting to see the differences in behavior between female and male offspring of cocaine sired rats. Male offspring of the cocaine sired rats showed less self administration of cocaine and reduced maintenance of self administration, however there were no differences in the reinforcing effectiveness of sucrose, indicating that this difference was not due to a learning deficit in the rats.  I would have expected the opposite of this result, and would have expected that offspring of cocaine sired rats would show more dependence for cocaine. BDNF protein expression may underlie the behavioral differences in these rats. High BDNF levels in the mPFC have been associated with counteracting the reinforcing effectiveness of cocaine, meaning high levels of BDNF would cause rats to reduce self administration and maintenance of cocaine.

            This finding is interesting to me because if it was possible to alter levels of BDNF protein in human mPFC’s prior to exposure to cocaine, this could increase resistance to drugs and decrease the potential for addiction. This paper was particularly interesting because it outlined an epigenetic mechanism behind the reduced cocaine reinforcement seen in the male cocaine sired rats, which was increased acetylation of histones. It was also interesting that the male offspring had decreased cocaine reinforcement because in human studies of genetics and drug addiction, it is often thought that drug addictions can be inherited from parents and this animal model shows the opposite when focusing on paternal effects of cocaine self-administration. It would be interesting to propose a future study in which the effects of both maternal and paternal cocaine self-administration were investigated to see if there is an effect on offspring of having both parents become addicted prior to mating.