2019 Biopsych Seminar Thursdays

I really enjoyed learning about an area of neuroscience and microbiology that I don’t typically read about. The interaction between gut and brain has definitely been a hot topic in the last few years, and it’s exciting to see robust research published linking the two in development and manifestation of psychological disorders. At my last co-op, we started to work on a mouse model of Parkinson’s disease in which pathology-inducing alpha-synuclein is injected peripherally and travels (presumably via the vagus nerve) to the midbrain and cortex! This is in the context of findings that alpha synuclein aggregates can originate in the gut and induce aggregation in the cortex and midbrain. I found the Buffington et al. paper much easier to follow and digest (no pun intended), and that’s likely at least in part why I preferred this one to the Reber et al. paper. The use of heat-killed bacteria was a great way to delineate vagus /gut interactions from immune response to the bacteria. It’s ...

This week's two papers both addressed understudied issues surrounding cocaine addition in a rat model, with the Holly group examining the influence of sex differences, including different stages of the estrous cycle for female rate and the Vassoler group unpacking sex-specific paternal epigenetic influence on F1 acquired cocaine addiction. I was disappointed while reading the Holly paper to discover that the only significant effects of estrous cycle in female rats was related to increased locomotion (walk duration) and not on actual dopamine levels in the nucleus accumbans or measures of a cocaine binge. Essentially, it seems that estrous cycle does not actually significantly impact the severity of a cocaine addiction on a neural system or behavioral level, but only heightens the response to the same dose of cocaine. The effect of stress, however, on both males and females but particularly on female cocaine addiction is quite shocking, but not surprising. Drug abuse is more frequ...

 This week’s paper investigated sex differences in addiction behavior. Sex differences always reveal hard to probe as there are usually many confounding factors. Holly et. al (2012) looked at differences in stress induced increased addictive behavior in response to cocaine. One of the most important factors accounted for in this paper was the phase of the estrous cycle in females. This allowed for the observation that females in the estrous phase of the cycle respond differently to cocaine when compared to both males and females in the diestrus cycle. Specifically, cocaine addiction is facilitated in this phase. Cycle specific DA levels in the NAcc were, unfortunately, not probed. This limits the conclusions that can be taken from the correlational observations made. Those effects should be investigated, along with direct manipulation of estradiol levels to determine if there is cause-effect relationship by which estradiol facilitates cocaine addiction by inducing DA signaling ch...

I found it unsurprising that female rats would have dopaminergic tone mediated by the presence of estradiol, and that this was not the case for castrated males. Recent studies show that females have a harder time dealing with chronic stress. This goes in line with the idea that the neuro-endocrine and neurobehavioral changes associated with female rats take place on a longer time scale. This explains the sustained dopamine elevation after stress since this might be a compensatory mechanism to prevent the negative symptoms of long lasting and chronic stress. This model might make sense from an evolutionary perspective. Males, having aggressive phenotypes and presence of testosterone, may be unlikely to feel chronic stress since they have a means of protecting themselves, while females do not. Thus males encounter acute stress and as such their baseline dopamine elevation after stress and cocaine administration spike for shorter duration but with great intensity.

Even as society learns to accept people with physical disabilities and other mental illnesses, drug addicts and their addiction are still too often stigmatized and trivialized. This is especially pertinent to women, who, at all stages of addiction, display more severe behaviors compared to men. To examine this gender difference, experimenters turn to rats. Holly et al. (2012) sought to find sex differences in behavioral and neural cross-sensitization, and cocaine binging behavior, as a result of episodic social defeat stress. It was interesting to see their implementation of a social defeat paradigm on female rats since  studies that study only male aggression (like the ones we’ve seen in past papers) lacked generalizability. In previous class discussions, the possibility of taking advantage of innate maternal drives to model female aggression. So, I thought it was a pleasant surprise to see this current study use lactating dams as the “resident” in the paradigm. The researchers a...

            The papers this week seem to be less directly connected than most of the previous pairings. While Vassoler  et al.  (2012) explored paternal epigenetic inheritance, Holly  et al.  (2012) focused on sex differences in behavior as a result of stress. The main similarities between these papers was their use of cocaine, their use of rats (different types, I might add), and the examination of some sex differences. Each paper made for interesting reading. As I mentioned before, Vassoler  et al.  examined the effects of chronic cocaine exposure to male rats on their offspring. They did this by exposing male rats to unlimited cocaine (or saline) for 60 days, then allowing them to mate. The offspring (F1 generation) were then allowed to grow and tested for cocaine resistance, learning deficits, and changes in neurochemistry. Vassoler  et al.  found that cocsired males seemed to exhibit a resistance to cocaine...

In the articles this week Holly et al. and Vassoler et al. investigated how environmental exposure to stress and genetic predisposition may lead to enhanced susceptibility to cocaine addiction. Interestingly both studies separated the mice by sex to observe sex specific differences in cocaine addiction. Holly et al found that episodic stress exerted a larger effect on female mice versus male mice. Compared to the stressed male stressed mice the female mice had a greater locomotor response to cocaine and longer cocaine binges than males. What I found most interesting about this paper was the discussion of gonadal hormones, specifically estradiol’s implication in enhancing susceptibility to addiction. The researchers took vaginal smears before each task, however concluded that only duration walking after cocaine administration was affected by estrous cycle. Holly et al suggest that in terms of cocaine binging, effects may not have been seen due to the fact that the binge spa...