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 (CINs) located within the NAc regulate dopamine release at the terminal; however, little research has been done to determine the precise role of CINs in the behavioral effects of opioids. To investigate the role of CINs in fentanyl consumption, we used chemogenetic (hM3Dq) stimulation of dopamine projections from the VTA to the NAc. Wildtype (WT) and heterozygous (HET) ChAT-Cre mice underwent intracranial surgery and were injected with a Cre-dependent viral vector to express the excitatory designer receptor hM3Dq in CINs of the NAc shell. Fentanyl seeking and consumption was tested using injection of a vehicle or clozapine N-oxide (CNO) and a 2-hour, operant fentanyl self-administration paradigm. After recovering from surgery, the mice were trained for 11 days to self-administer 10 ug/mL of fentanyl citrate. On days 12 and 14, the mice were injected with either a vehicle or CNO 30 minutes prior to operant conditioning. The current data suggest that there are no significant differences between the WT and HET mice. This could mean that striatal CINs are not implicated in fentanyl seeking behavior. Research investigating the role of CINs in other behaviors such as withdrawal could help determine the role of these neurons in substance use disorders. I plan to attend graduate school for clinical psychology with a focus in substance use disorders, so this research is largely related to my future career and research interests.
Author(s): Cambria Beane, Psychology and Neuroscience Major
Advisor(s): Anna Radke, Department of Psychology
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