Neuronal Excitability in the Medial Habenula and Ventral Tegmental Area Is Differentially Modulated by Nicotine Dosage and Menthol in a Sex-Specific Manner

• DOI: 10.1523/eneuro.0380-23.2024
• Publication Date: 2024-01-17T18:50:19Z
• Authors: Nathan A. Olszewski; Samuel Tetteh-Qua...; Brandon J. Henderson
• Keywords: 0301 basic medicine; 03 medical and health sciences; Research Article: New Research

The medial habenula (MHb) has been identified as the limiting factor for nicotine intake and facilitating withdrawal. However, few studies have assessed MHb neuronal excitability in response to nicotine, and, currently, a gap knowledge is present finding behavioral correlates region. Moreover, no study date evaluated sex or dosage factors of MHb. Here, we utilized an e-vape self-administration (EVSA) model determine differences between sexes with different dosages ± menthol. Following this paradigm, employed patch-clamp electrophysiology assess key metrics relation endpoints. We observed female mice self-administered significantly more than males, regardless dosage. also direct correlation behavior low-dose + menthol males. Conversely, high dose yields inverse males only. In addition, intrinsic ventral tegmental area (VTA) does not track amount self-administered. Rather, they correlate active/inactive discrimination mice. Using fast-scan cyclic voltammetry, that dopamine release dynamics are linked reinforcement-related motivation-related behaviors females. These results point sex-specific difference activity VTA leading distinct behavior. His could lend evidence clinical observations smoking nicotine-use differing