Holly et al

Knowing that stress plays a huge role in the vulnerability to drug addiction, Holly et al decided to study female and male stressed animals in relation to drug addiction.  They studied sex and estrous cycle differences in rats behavioral and dopaminergic cross-sensitization to cocaine, as well as cocaine consumption when provided with unlimited access self-administration.  The four measures used to assess this were locomotor activity in response to acute cocaine, in vivo micro dialysis of DA in the NAc in response to acute cocaine; cocaine consumption in self-administered binge, and vaginal smears for estrous cycle examination.  I really liked the format of this paper since the first page introduced to you their objectives measures and results in a very clear and concise manner to then get into the whole introduction and discussion of everything in a more detailed manner.

            The first part of the experimentation consisted of splitting the groups into stressed and unstressed.  The animals that were considered stressed were subjected to four defeats by animals of the same sex that had been observed to show aggressive behavior.  I am not really a fan of how this stress model works and believe that they could have done some behavioral tests to assure these animals were indeed stressed by showing some sort of depressive (not necessarily depressive but characteristic stressed symptoms) like symptoms.  Also, I am not really sure of why they decide to use same sex for the agresive paradigm, and if they ruled out anything specific of combining sexes.  I might think that in human populations having males be aggressive with females can be very stressful, but this might indeed be what they are aiming for. As it is typical for people of stressful households, them being with abusive parents or spouses to be vulnerable to drugs. However, I understand the fact that they are using this model from previous research which has already been shown to increase cocaine addiction etc.  Nonetheless, it would be really nice to see other type of stressors, maybe more longitudinal stressors or chronic mild stressors as to see how it affects.

I also find extremely interesting the fact that they focused on sex difference, since as we have seen in many other articles they rather stick to male animal models.  However, considering how different we have seen male and female brain behavior and development throughout history, I highly support these papers. Effectively they observed a longer duration of cocaine effects in females, than in males.  I was not amazed by the binge effects they saw in females being significantly longer than those in men, since as said before women have very characteristic behaviors such as binging more often than men.

I would have tried looking for more mice for the micro dialysis part of the study, since the small amount really limits the reliability of their findings. Moreover, they were aware of this. Also, it would have been interesting for them to use dopamine receptor blockers or reuptake blockers to see how this affects the dopamine levels.   I do not quite understand the effect of estrus on the stress, and would really encourage them to research about how this works biochemically and what is going on with the dopamine levels. Also, I would encourage them to a similar study but with longer time period as to see the effects on a longitudinal study as it was seen that female had cocaine effects for a longer period than male.