Skip to main content

Sex Differences in Cocaine Addiction in Rats

By
Addiction is a very interesting topic to me and I believe there is so much progress to be made in this field, making it very exciting in terms of research. I have done some clinical research in addiction during one of my co-ops at MGH in the pediatric psychopharmacology department. The clinical study was based on the comorbidity of mood disorders and substance use disorders in young adults and the effects of treating this mood disorder on the subject's substance use. While this correlation of improved substance use post-treatment of an underlying mood disorder seemed obvious to me, it is not a very well studied area. I was excited to dive into the Holly paper and learn about the effects of stress on addiction and drug response. The Holly et al. paper published in 2012 investigates the effects of episodic social defeat stress on cross-sensitization to cocaine. The central theme within this investigation were the sex differences among these effects and how the estrous cycle further changes the responses in female rats. After several introductions to the social defeat paradigm I was excited to read a study which implemented this model in both male and female mice, using a dominate male mouse and a lactating dam as the aggressors. Based on my knowledge of human addiction statistics and some of the information reported in the introduction, the results were somewhat of a surprise to me. In the introduction, it is stated that in 2010 35.9% of cocaine users in the USA were female (SAMSHA 2010). Based on the results of this paper, females seem more susceptible to cocaine addiction, despite making up less of the using population. However, this is where stress comes in as a factor. Sex became a more differentiation factor amount stressed populations than in the male and female unstressed groups. The combination of stress and sex made females have a higher sensitization to cocaine measured with increased locomotion, increased levels of dopamine, and have a higher number of infusions with a longer "binge" than any other cohort, with even more dramatic results in females in estrous. Stressed males also showed increased sensitization and use compared to the non-stress group, however the results were more robust in female rats, alluding to a significant finding for addiction medicine. With addiction being generally more prevalent in males, this study led me to contemplate the effects of why addiction occurs in people. While males may make up a greater percent of users, females have a greater likelihood of becoming binge users and a higher predisposition to relapse. I am curious about the data on stress in these females users and the motivation to begin using.
The Vasselor et al. paper published also in 2012, took a different approach to sex differences in cocaine addiction, studying the potential for epigenetic to facilitate the inheritance of a cocaine-resistance phenotype. While in humans we have narrowed down a predisposition to addiction (or other risk taking behaviors) to a gene loci, I have never learned about epigenetic factors of such a complex and multifaceted behavior. Based on the results of this paper, Vesselor and their team was able to show an increase in cocaine-resistance in male rates who's paternal predecessor was exposed to cocaine. The cocaine resistance was observed both in quantity and duration of self-administered cocaine. I appreciated the amount of "rule-out" experiments preformed by this group in order to more closely observe the effects of cocaine exposure in a parent as opposed to co-founding variables. They were able to show more certainly that there effects were due to changes in BDNF protein concentration in there brain rather than paternal involvement with the mother, generalized learning deficits in the pups, or decreased sucrose preference. With information pointing to the possibility of epigenetic playing a role in addiction we can look more closely at the cause of substance use disorders at a clinical level. In addition, the information provided in this paper showing changes in protein levels affecting resistance and maintenance of drug addiction, provides forward progress to treatment options for those with substance use disorders.












Comments

Post a Comment

Popular posts from this blog

Week 2- Dopamine Modulation of Depressive-like Behaviors

By
The Chaudhury et al paper explored the neural circuit mechanisms involved in the dopamine modulation of certain symptoms of depression. In this study, the researchers looked at social interaction and sucrose preference as part of their social-defeat paradigm, which has been shown in the past to be indicative of depressive-like behaviors. Although I initially did not completely see the connection between the social-defeat stress model of depression and the tonic vs phasic firing of dopamine neurons, it seemed that susceptibility and resilience to stress played a role in the functional/behavioral effects of dopamine firing. It was interesting to see how chronic mild stress with phasic firing of VTA dopamine neurons converted even resilient mice into susceptible mice.  The Tye et al paper similarly looked at the dopamine modulation of depressive-like behaviors, focusing on motivation with the forced swim tests and open field tests, followed by measurement of anhedonia by quantifyi...
Post a Comment
Read more

Sial & Allsop

By
Sial et al. derived a novel approach for studying what they deem vicarious defeat stress (VSDS) as a model for MDD, PTSD, and other mood-related disorders as an alternative to the classical CSDS paradigm. Using adult male mice, they demonstrate that their model induces a robust and measurable social avoidant phenotype as well as other stress and anxiety related behavioral outputs. Their subsequent rescue study with chronic fluoxetine treatment shows reversal of the behavioral phenotypes and emphasizes the predictive validity of the model. Allsop et al. found that BLA-projecting ACC neurons preferentially encode socially derived aversive cue information by encoding the demonstrator’s distress response during observational learning, hence enabling acquisition of negative valence of cue by BLA neurons and behavioral output. In order to test their hypothesis, Allsop et al. used an observational fear conditional paradigm to create association between a conditioned stimulu...
Post a Comment
Read more

Buffington and Reber

By
Buffington et al. explore a mechanism by which maternal obesity can induce neuronal and subsequent behavioral disorders. Using a model of high-fat diet (MHFD)-induced obesity, the authors showcase the strong connection between the brain and the gut, and its impact on behavior. The findings are provocative; by exposing these offspring to the microbiome of control offspring, there was evidence of a rescued observed behavioral phenotype. Furthermore, a phylogenetic profiling of the gut microbiome revealed a decrease in L. reuteri within MHFD offspring, and introduction of live L. reuteri into the drinking water shows successful rescue of the behavioral issues in the MHFD offspring. L. reuteri-induced expression of oxytocin within the paraventricular nuclei of the hypothalamus provides a potential mechanistic explanation for the behavioral changes. I thought this paper provided robust support for the hypothesized interaction between the gut biome and the developing CNS, with tremendous po...
Post a Comment
Read more