Venniro et al used a more fully encompassing approach to addiction research by introducing an operant volitional model of social reward and drugs. The researchers used mostly both male and female rats, however, for some experiments, like the bingeing model, they only used male. I thought this was interesting; if they were already running studies with both sexes, why not use both for all experiments? Expecially given that our last paper demonstrated that there are sex differences in addiction, and that female rats can be more susceptible after a stressful event. Despite this, I appreciated that the researchers approached addiction from a more human standpoint. When in a laboratory, it can be hard to model the human experience, but introducing a volitional social paradigm is one step closer as for many addicts, social factors play a pivotal role. While the last papers we read showcased the negative side effects of bad social interactions, this article focuses on rewarding social interactions and its protective effects against addiction and relapse. The model consisted of a rat that was trained to level press for a drug, or another level that allowed them to receive social interaction with a fellow rat. I did not see in the paper what kind of social interaction was administered, but I would have liked to potentially compare the outputs. A social interacting involving a rat of the opposite sex and mating may have a different rewarding effect than interacting with a littermate. Regardless, the interaction was evidently rewarding because the rat chose the social interaction lever significantly more than the drug administration lever, and this effect was maintained for up to 4 weeks. I think this model is more applicable to human addiction than many other animal models as it takes into account the potential for a social support and network to help in recovery. That being said, there are of course differences, which the authors do somewhat address in their discussion. For humans, social reward like Community Reinforcement Approach (CRA) can be extremely beneficial and positive, however, there are many more complicated factors that come into play in humans that may not be there for rats. For an individual that may have addiction and may be depressed, social interaction could be a negative experience instead of a rewarding one. Still, I think this model is a valuable one and gives valence to the benefits of a strong support system and behavioral based therapies. Lastly, I would have liked the authors to potentially explore more neural correlates. They examined the amygdala and the activation of neurons and found that social-induced choice abstinences inhibited the incubation of craving on a neural level using C-FOS. I would have liked to have seen reward pathway activations as well, potential to see if more DA neurons in the VTA or Nucleus accumbens were activated in response to social interaction and drugs. However, as the next article points out, the CeA plays a pivotal role in addiction.
De Guglielmo et al focuses on a more neural mechanistic approach to a rat model of alcohol addiction. For this model, the CeA CRF neurons were optogenetically inhibited. CeA CRF neurons are activated during drug withdrawal. Behavioral tests were also used to assess withdrawal symptoms and an open field test looked at anxiety. Ultimately, this study used an optogenetic model to find a neuronal ensemble including the CeA CRF neurons that project to the BNST that is responsible for withdrawal and driving high levels of drinking. When these neurons are inhibited, rats do not express as much withdrawal and decrease escalation in drinking. I thought that this study was very thorough in showing that the optogenetic manipulation was working and doing what it wanted to and combining the behavior with the mechanistic biological results. Not only did they show neuronal firing, but also outputs like alcohol intake or distance travelled. However, the behavioral measures for withdrawal were not all remedied as only 2 of the 5 were ameliorated. I wonder why those withdrawal signs remained and if it is working by a different neuronal mechanism than the CeA BNST pathway. It was interesting to see that the overall beneficial effect was reversible by just turning the laser off, and led me to wonder if there could be a way to utilize activation of neurons to change plasticity. I wonder if you were to continually fire neurons, that their synapses would be enhanced, and potentially create a protective effect longer term. This could be extremely relevant to addiction, where withdrawal is extremely difficult to get through and a prolonged treatment may be more necessary. The authors do discuss how this could be very relevant to clinical applications as this neuronal ensemble/pathway would be a potential target for treatment. However, again we encounter the challenge of translating the animal studies to humans. While the first article is more easily translated because social interaction is more achievable, we cannot optogenetically activate a human's brain (yet). Still, I think that this lends value to understanding a disorder that has not been understood in the past and giving it a neuronal basis and a potential neuronal remedy. Lastly, I wish that this study had included female rats like the one before. The more research we encounter, the more we understand the importance of including both sexes, especially within addiction.
Comments
Post a Comment