The Ventral Tegmental Area and Medial Habenula Differentially Control Reward, Reinforcement, and Intake of Nicotine

Abstract

<b>Abstract ID 20494</b> <b>Poster Board 335</b> For years, prior research has established the scientific premise that the ventral tegmental area (VTA) and the medial habenula (MHb) mediate aspects of nicotine reward, reinforcement, aversion, and intake. To examine how both the VTA and MHb are involved in nicotine reinforcement-related behavior, we used genetically modified mice (males and females) that express fluorescent nAChRs in a mouse model of vapor self-administration. Mice were trained to acquire self-administration on a FR1 and FR3 schedule using nicotine with or without flavors (menthol or green apple). Green apple and menthol enhanced nicotine vapor self-administration in both male and female mice but in a sex-dependent manner (males at 6 mg/mL nicotine and females at 60 mg/mL nicotine). Following vapor self-administration, brain slices containing the VTA and MHb were prepared to examine self-administration-induced changes in baseline firing and intrinsic excitability. To examine intrinsic excitability, we used a current-step protocol to determine rheobase (current necessary to elicit an action potential) and maximum spikes during current steps. We correlated FR3 active nose pokes (mean of 5 FR3 sessions) to electrophysiological measures to examine how neuronal excitability in the VTA and MHb was linked to reinforcement-related behaviors. We observed that intrinsic excitability of VTA dopamine neurons did not correlate to FR3 active nose pokes; but it did correlate to active and inactive nose poke distinction. We observed that the intrinsic excitability of medial MHb neurons correlated inversely to FR3 active nose pokes (high FR3 nose pokes, lower intrinsic excitability). Correlations were consistent between unflavored or flavored nicotine assignments; but menthol and green apple exhibited greater changes in intrinsic excitability of neurons. These data suggest that the MHb may be critical for the magnitude of nicotine intake while VTA dopamine neurons may regulate the learning-related behavior associated with nicotine intake. This work was supported by funding from the National Institutes of Health (DA050717 and DA046335 to BJH).