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Addiction: Venniro et al (2018) & de Guglielmo et al (2019)

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Venniro et al. 2018 presented a novel and interesting approach to the treatment of addiction by incorporating a social element. I found the introduction by the authors quite compelling as they introduce their subject of study and provide a in depth explanation as to why they decided to study social interaction as a factor for drug addiction mentioning how this idea of social interaction reducing drug administration maps on to human behavior such as the CRA and support groups providing protective measurements for relapse. Normally introductions of papers just mention the paradigms and hypothesis used and generally conclude with “this is a novel route that has not been tested before” or “based on prior research we assume this will happen”. However, Venniro et al. took the time to provide a substantive explanation as to how their hypothesis and model are relevant and how they can provide clinical treatment in humans. I appreciated the vigor with which they approached their model. An element I was quite skeptical about was the ability of scientists to determine addiction- like phenotypes in rats based on DSM-IV criteria. The DSM, although currently the only basis we have to diagnose patients, still is ever changing and debated on. Therefore, I highly doubt its transferability to a different species entirely. Perhaps because you can measure the dosage of substance, it allows for some quantitative measurements and criteria, however this would never be possible with something like depression or anxiety. I liked that they attempted all of their experiments with human patients and behaviors in mind and they made an effort to draw out the parallels, however the level with which we can compare the same phenotypes across different species is debatable. Although we try our best to model the human experience in animal models, there are limits where expression of phenotype based on some intrinsic stressor will differ across organisms and so I am unsure about the ethological validity of this paradigm. This is, still, the closest paradigm I have seen that models human addiction well. Based on last week's papers, it is evident that there is some difference in addiction between male and female rats, so I was quite curious when the authors found their hypothesis supported using male and rats and heroin, but only male rats and methamphetamine. I assume they tested the female rats and did not find any interesting or supporting evidence, but they did not mention the female rats at all which was quite surprising as I would like to see what they found even if it was contradicting data. 

De Guglielmo et al. 2019 approached the subject of alcohol addiction or abuse. Their study focused on the central nucleus of the amygdala, known to harbor neurons suggested in alcohol related memories. I found it quite interesting that they were able to isolate a local population of neurons that were prominently involved in withdrawal and drive for drinking. Normally, things like addiction and substance abuse are usually looked at from a genetic standpoint and it has been shown to be something of a polygenic trait when heritability was taken into account. But in terms of how exactly it manifests in the brain is something I am new to. Therefore, the results presented by the authors were of great intrigue to me. Using optogenetics to inhibit the CRF neurons in the CeA lead to reduced drinking in dependent rats and partially alleviated withdrawal symptoms. This major finding of the paper is really fascinating and has made me think about the possible implications for treatment. Using pharmacology to target circulating corticotropin releasing factor may have some effect on these neurons in the CeA. The authors mentioned the use of a CRF1 receptor antagonist and I wonder whether anyone has begun research on whether this alone could act as a drug to reduce elevated drinking and withdrawal effects. An aspect that eluded me was why we saw the reversible decrease in dependent rats and not control rats. What about the dependent rats made them different? This suggests that this mechanism or treatment (using opto) is only useful for dependent rats or in a human patient only those that can be considered addicts. This is a part I was confused about and I would like to understand further, why we see significant decreases in drinking in only the dependent rats. 

Overall both papers were highly interesting and approached the subject of addiction from two very different perspectives. I think the integration of social interaction (support groups, AA meetings, 12 step programs) and the possible pharmacological intervention (maybe one day optogenetics for humans) may lead to a highly efficient and functional treatment for substance abuse and addiction. I also think predisposition to addictive behavior as discussed last week is highly relevant to this discussion of clinical treatments. 

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