Comparative Analysis of Dopamine Neuron Activity in Pavlovian Versus Non-Contingent Methamphetamine Exposure

Abstract ID 95965 Poster Board 124 There is a notable increase in methamphetamine abuse. Despite this increase, the distinct impacts of environmentally associated (Pavlovian) and non-contingent (uncoupled) methamphetamine exposure on the activity of midbrain dopamine neurons and the dynamics of neuronal networks are not well understood. Our data suggests that acute non-contingent exposure to methamphetamine increases firing rate of dopaminergic neurons and alters neuronal network dynamics, evidenced by increased synchrony, modularity, and assortativity (N = 5, p < 0.05). However, the effects of exposure to methamphetamine in an environmentally conditioned versus an unconditioned context on dopamine neurons remain unknown. Our data, and the literature, support the hypothesis that Pavlovian versus uncoupled methamphetamine exposure influences dopamine neuron activity and neuronal network connectivity in distinct ways and differential mechanisms. In the current study, male and female mice were administered methamphetamine (2mg/kg, intraperitoneally) or saline, either through a conditioned place preference paradigm or in their home-cage environment. Forty-eight hours after the last drug administration, we employed ex vivo patch-clamp electrophysiology to measure the baseline firing activity of dopamine neurons in the ventral tegmental area (VTA). Our data indicates that forty-eight hours after the last drug administration non-contingent administration of methamphetamine increases the baseline firing activity of VTA dopamine neurons (n = 6, p < 0.05) and leads to sensitization upon exogenous methamphetamine application (n = 6, p < 0.05). This effect could potentially be attributed to the desensitization of inhibitory D2 receptors. Current studies are exploring whether environmentally conditioned drug exposure similarly or differently influences the baseline activity of dopamine neurons and examining potential sex-dependent responses in each drug exposure model. This research offers important insights into the neurobiological effects of various methamphetamine exposure models in the context of developing pharmacological treatments for patients.