The organization of the Venniro paper was extremely frustrating. At first read, the experiments seem to be laid out nicely with the subheadings, but the procedures and results were all over the place. It was so difficult to figure out the details of the methods, even with the supplementary note. I felt like some of the tests, or lack thereof, were random. Why, for instance, did they calculate addiction scores in two different ways? Why were females only used in two of the experiments that they performed? I felt like the researchers were trying to put a lot into this paper so that their conclusions could be significant, but it all felt a little bit messy to me. That being said, they did a good job at establishing a voluntary model that is more indicative of human behavior than previous forced abstinence models. As mentioned at the end of the paper, there are still several differences between this model and addiction in humans, but incorporating a social aspect is important. In addition, there are more confounding factors that I would like to see tested in this model. For example, if we depressed or stressed an animal, would they have the same preference for social interaction over drug administration? Social reward does not outperform drug administration in people, so I’d be interested to see if we could test other factors. I think, given the results from experiment 5, that there are several implications of this study. If we establish a pathway involving the PKCδ neurons in a similar experiment as the de Guglielmo paper, we could potentially find better targets to treat addiction. I’m also extremely curious as to if the PKCδ neurons were also activated when testing for heroin, since that is a different class of drug that seemed to have a similar result in regards to social choice as methamphetamine did. In the de Guglielmo paper, they didn’t look at PKCδ either, and I’d be curious as to if these neurons were also activated in alcohol addiction.
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...
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