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Venniro et al. 2018 and de Guglielmo et al. 2019

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The article by Venniro and colleagues examined the role of volitional social interaction as a means of preventing drug seeking in addicted rats. This paper used methamphetamine and heroin as their drugs. I found this paper incredibly difficult to follow, partially due to the Nature Neuroscience organization, but mostly because it seemed like this was a jumble of conclusions. It seemed like perhaps this paper was written when the authors looked at datasets from old experiments and saw a chance to pull patterns they observed into one publication instead of running a new experiment to test that observation. That aside, I found the findings of this study a little odd and unexpected. It was my understanding that most people first experiment with drug taking in social situations due to social pressures to participate. So, when the authors reported that receiving a social reward would attenuate choice to use drugs (both methamphetamine and heroin)—that rats would choose social rewards over drugs nearly 100% of the time—I was shocked. More shocking, though, was that any changes in behavior in response to social reward punishment or lack of reward were not at all related to addiction scores. That finding made me question the reliability of the criteria used to determine each rat's score, but then it made me think about the DSM criteria for diagnosing humans with addiction. Overall, my biggest concern for this paper was its ability to translate the findings to rats to any viable clinical outcome in humans. Why, if faced with the choice between continuing drug use and maintaining a relationship with family, for example, do so many drug addicts continue to use? Clearly social reward is not weighted equally between humans and rats, or even across all humans for that matter.

The article by de Guglielmo and colleagues focused more so on using optogenetics to manipulate pathways thought to underlie addiction as a means to prevent alcohol seeking and decrease withdrawal symptoms. Similar to the papers we read last week, de Guglielmo and colleagues point to CeA projections to the BNST as a key pathway in maintaining addiction. The authors took this one step further and determined that corticotropin-releasing factor neurons are a critical component of this pathway. The possibilities for translating these findings into clinical practice are far clearer in this study than they were in the Venniro et al. article. The CRF Cea-BNST pathway could potentially be a target for pharmaceutical intervention or maybe surgical intervention (Is deep brain inhibition a thing? If not, it should be.) to treat patients with severe alcohol addiction that is resistant to treatment with traditional methods, like CBT. In Clinical Neuroscience, we discussed a drug that is used to treat alcoholism (Antabuse) by creating a very unpleasant reaction to even the tiniest drop of alcohol, even in everyday items like mouthwash. That kind of treatment has strong, likely undesired, effects on a person's general daily life, so it would be awesome to be able to improve treatment to the point that an addict simply doesn't have the desire to consume a drug that they previously had a poor relationship with. However, this study was specifically investigating alcohol addiction, so it isn't necessarily true that this pathway would also be implicated in all types of addiction (or even substance use).

I still have one major question after now reading 4 papers about addiction. Drugs of abuse were used in all of the studies we examined, but I am curious how each of the results might differ with addiction non-pharmacological things. Many humans are addicted to gambling, pornography/sex, shopping, or plastic surgery (just to name a few). How are "behavioral" addictions different? Do they activate the same neuroanatomical pathways? Can they be reversed with the same mechanisms? I would imagine that isn't the case, but it would be very difficult to research considering rats and mice don't really get lip injections and butt implants, and rodents definitely don't have money to blow on designer bags. It doesn't seem too far fetched to train rodents to gamble for something like fruit loops, so maybe that could be a way to test behavioral addictions in the future.

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