Skip to main content

Sex Differences in Drug Abuse

By

March 30 Papers (Holly et. al, Vassoler et. al)

Holly et. al’s 2012 paper explores the sex differences in neural and behavioral cross-sensitization to cocaine following social defeat stress in rats. The study found that while both sexes develop this cross-sensitization, the effect is larger and lasts longer in females, possibly due to estrogens and their role in modulating mesocorticolimbic dopaminergic function. Additionally, female rats consumed more cocaine than male rats after undergoing the social defeat stress paradigm. 

These findings could have great clinical relevance in developing treatments for drug addiction in humans, particularly for women who have a heightened vulnerability to cocaine addiction, use the drug more often than men, and are more likely to relapse. Perhaps the development of treatments for drug addiction in men and women should be carried out separately if it isn’t already, and should focus on mesocorticolimbic dopaminergic function, with special consideration to how it is affected by estrogen in women. Moreover, children often inherit a susceptibility to drug addiction from their parents, and it would be interesting to know whether women are more likely to inherit this susceptibility from their parents than men, or inherit it to a larger degree. Taking it one step beyond stress, I’d be curious to read research regarding the neural or biological mechanisms behind how stress-related disorders such as anxiety or PTSD and increase vulnerability to drug addiction.

On the other hand, Vassoler et. al’s 2013 paper examines the epigenetic inheritance of a cocaine-resistance phenotype in the offspring of male rats that had been allowed to self-administer cocaine during spermatogenesis. The results of this study showed delayed acquisition and decreased intake of cocaine in the male, but not female, offspring of these rats. Furthermore, Vassoler et. al found that there was an increase in Brain Derived Neurotrophic Factor (BDNF) mRNA and BDNF protein in the medial prefrontal cortex (mPFC) of the cocaine-resistant male offspring, as well as an increase in association of acetylated histone H3 with BDNF promoters. The paper claimed that this might be at least partially responsible for the expression of the cocaine-resistance phenotype. 

I find the idea that what could be described as “life experiences” such as using drugs or undergoing famine can alter the genetics of offspring even just one or two generations down the line to be fascinating. What stands out the most about the conclusions drawn by this paper is that the inherited resistance to cocaine seen in the rats in this experiment directly contradicts what research has shown regarding how, in humans, the children of heavy drug users are often born with a susceptibility to drug addiction. It would be interesting to learn more about what underlies this difference between rats and humans in the genetic inheritance of drug-related susceptibility. Although I do not know how plausible this would be, these results make me wonder whether increasing association between BDNF promoters and acetylated histones and increasing BDNF mRNA and protein in the mPFC of humans addicted to cocaine, or their children, could potentially be an avenue of treatment for drug addiction. Finally, even though the paper gave valid reasons as to why only the offspring of male cocaine-using rats were studied in this experiment, it would be great if researchers could find a way to test whether the results of this study would be replicated in the offspring of female cocaine-using rats, especially given that as previously stated, women are more vulnerable to cocaine addiction. 

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