Both Holly et al. and Vassoler et al. examined neurobiological and behavioral sex differences in cocaine use in rats. However, that is the extent of the similarities between the two paradigms.
Holly and colleagues used a social defeat stress method in which male and female rats were defeated by a rat of their respective sex—either a larger male rat or a lactating dam—using the resident-intruder method of social defeat. This is the first instance of female social defeat stress we have seen this semester, which was really exciting! The rats then underwent one of three experiments to examine behavioral sensitization to cocaine (increased locomotion), neural sensitization to cocaine (microdialysis of DA in the NAcc), or cocaine binge (unlimited access to cocaine). Stressed rats were compared with non-stressed controls of the same sex. I really appreciated how thorough the experimental setup was, but I think the unrestricted cocaine availability was probably not the most accurate model of the real world. It might have added another perspective if there were a fourth experiment in which the rats had to successfully perform a behavior or wait a varied amount of time before they could receive more cocaine, since people generally have limited drug access and have to complete other tasks to seek out drugs. Additionally, I think it was really awesome to see a social defeat paradigm that used females, but I was curious how other types and durations of stress may have impacted the results. If there was time and an unlimited number of rats, it would be cool to see multiple groups of stressed rats. Some rats could undergo chronic mild stress, or maybe another paradigm where rats had food insecurity or were in a dangerous home cage, perhaps.
One thing I noticed from the Holly et al. paper is that cocaine didn't seem to have much effect on males. I understand that the point of this paper was to highlight the more extreme behavioral and neural changes in females, but I was confused why, evolutionarily speaking, males are not as sensitive as females (behaviorally or neurally). In my psychopharmacology class, we have talked a lot about how drug receptors exist because there is an endogenous chemical that binds that receptor. What is the evolutionary benefit of males being less sensitive to endogenous opioids that resemble cocaine?
The Vassoler and colleagues study was also quite interesting. The authors examined how paternal cocaine exposure effects cocaine taking in offspring of different sexes through both behavioral drug seeking (lever pressing) and biological (neural structure and sperm contents) factors. Vassoler et al. found that male offspring sired by cocaine-using fathers took longer to initiate cocaine taking and did not maintain self-administration of the drug, while females showed no difference in administration latency or maintenance regardless of paternal cocaine use. Physiologically, Vassoler and colleagues found differences in limbic system BDNF levels (which is related to reinforcement), size of the BNST (which is related to stress and addiction susceptibility), and sperm epigenetics between male and female offspring, which may explain some of the behavioral differences between the two. I was really glad that I read this article second because this information was useful in creating my own explanation behind some of Holly et al.'s findings.
Holly and colleagues used a social defeat stress method in which male and female rats were defeated by a rat of their respective sex—either a larger male rat or a lactating dam—using the resident-intruder method of social defeat. This is the first instance of female social defeat stress we have seen this semester, which was really exciting! The rats then underwent one of three experiments to examine behavioral sensitization to cocaine (increased locomotion), neural sensitization to cocaine (microdialysis of DA in the NAcc), or cocaine binge (unlimited access to cocaine). Stressed rats were compared with non-stressed controls of the same sex. I really appreciated how thorough the experimental setup was, but I think the unrestricted cocaine availability was probably not the most accurate model of the real world. It might have added another perspective if there were a fourth experiment in which the rats had to successfully perform a behavior or wait a varied amount of time before they could receive more cocaine, since people generally have limited drug access and have to complete other tasks to seek out drugs. Additionally, I think it was really awesome to see a social defeat paradigm that used females, but I was curious how other types and durations of stress may have impacted the results. If there was time and an unlimited number of rats, it would be cool to see multiple groups of stressed rats. Some rats could undergo chronic mild stress, or maybe another paradigm where rats had food insecurity or were in a dangerous home cage, perhaps.
One thing I noticed from the Holly et al. paper is that cocaine didn't seem to have much effect on males. I understand that the point of this paper was to highlight the more extreme behavioral and neural changes in females, but I was confused why, evolutionarily speaking, males are not as sensitive as females (behaviorally or neurally). In my psychopharmacology class, we have talked a lot about how drug receptors exist because there is an endogenous chemical that binds that receptor. What is the evolutionary benefit of males being less sensitive to endogenous opioids that resemble cocaine?
The Vassoler and colleagues study was also quite interesting. The authors examined how paternal cocaine exposure effects cocaine taking in offspring of different sexes through both behavioral drug seeking (lever pressing) and biological (neural structure and sperm contents) factors. Vassoler et al. found that male offspring sired by cocaine-using fathers took longer to initiate cocaine taking and did not maintain self-administration of the drug, while females showed no difference in administration latency or maintenance regardless of paternal cocaine use. Physiologically, Vassoler and colleagues found differences in limbic system BDNF levels (which is related to reinforcement), size of the BNST (which is related to stress and addiction susceptibility), and sperm epigenetics between male and female offspring, which may explain some of the behavioral differences between the two. I was really glad that I read this article second because this information was useful in creating my own explanation behind some of Holly et al.'s findings.
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