Cue reactivity of non-dopamine neurons in the midbrain

Poster Session F - Tuesday, April 16, 2024, 8:00 – 10:00 am EDT, Sheraton Hall ABC

Varun Nair¹ (vsn7@pitt.edu), Collin Lehmann², Khaled Moussawi²; ¹University of Pittsburgh, ²UPMC

An influential model of addiction proposes that repeated exposure to addictive drugs results in overvaluation of drug cues and long-lasting cue-drug associations, which results in heightened motivation to seek drugs upon exposure to these cues. This model focuses on the role of midbrain dopamine neurons in forming these associations, known as cue reactivity. However, the neurophysiological responses of non-dopamine neurons to cues predicting opioids vs. natural rewards have not been examined previously. Multi-unit electrophysiological recordings were collected from the midbrain of adult Long-Evans rats during Pavlovian presentation of cues associated with the opioid remifentanil vs. oral sucrose. Non-dopamine neurons were identified using an automated hierarchical clustering algorithm. Our data identify a subpopulation of non-dopamine neurons that shows significant cue reactivity in response to opioid or sucrose cues. These neurons fire almost exclusively in dense bursts and are inhibited by sucrose or remifentanil reward. However, they show an immediate initial phasic activation response being much faster than the phasic response observed in putative dopamine neurons. Additionally, this subpopulation shows enhanced response to opioid vs. sucrose cue within the same neurons, and to sucrose cues in drug-exposed vs. drug naïve animals. Another subpopulation was identified which exhibit immediate inhibition to sucrose cues, however it was only identified in drug naïve animals. One more subpopulation with persistent activation throughout the cue period was observed. Our results demonstrate cue reactivity in non-dopamine neurons in the midbrain. Next steps involve establishing the identity of these neurons and their role in drug seeking behavior.

Topic Area: METHODS: Electrophysiology