The opioid epidemic is a significant public health crisis in the United States with a growing number of overdoses related to illicit opioids such as fentanyl. Ohio, in particular, has been greatly affected. One of the neural circuits implicated in opioid-related behaviors is the mesolimbic dopamine system –a reward pathway involving the ventral tegmental area (VTA) and the nucleus accumbens (NAc). Cholinergic interneurons exist in the NAc, and they reduce dopamine release when they are active, countering motivated and reward-related behaviors. Located on these CINs are u opioid receptors (MORs) which could interrupt CIN firing, resulting in heightened opioid-induced reward. However, the exact role of CINs in the behavioral effects of opioids has never been investigated. To study these CINs, we used a Cre-dependent transgenic approach to delete the MORs on cholinergic cells, resulting in Cre+ mice that had the MOR deletion (experimental group) and Cre- mice that had intact CINs (control group). Opioid consumption was tested using a 2-hour, operant fentanyl self-administration paradigm over 28 sessions. Preliminary data suggests no significant differences between mice that do and do not have the MOR on cholinergic cells. If this result holds true with further replications, it could mean that cholinergic cells are not implicated in fentanyl seeking. With more specific and targeted approaches such as chemogenetics, it would be interesting to target other specific MOR-expressing regions, such as the amygdala and thalamus, for their role in fentanyl seeking. I plan to attend graduate school for psychology, so this research gave me valuable experience writing a research proposal, conducting research, analyzing results, and presenting to various audiences.
Author: Cambria Beane, Psychology and Neuroscience
Advisor: Anna Radke, Psychology
Graduate Advisor: Sean Monroe, Psychology
You must be logged in to post a comment.