Vesicular glutamate transporter 2 expression in the ventral tegmental area of outbred male rats following exposure to nicotine and alcohol

• Published in: Drug and alcohol dependence reports Vol. 8; p. 100180
• Main Authors: Vrettou, Maria, Thalhammer, Stefan Bernhard, Svensson, Anne-Lie, Dumas, Sylvie, Nilsson, Kent W, Wallén-Mackenzie, Åsa, Fredriksson, Robert, Nylander, Ingrid, Comasco, Erika
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2023; Elsevier
• Subjects: alcohol; brain; expression; Full Length Report; nicotine; Vglut2; alcohol; nicotine; expression; brain; Vglut2
• ISSN: 2772-7246; 2772-7246
• DOI: 10.1016/j.dadr.2023.100180

•More dopaminergic-only neurons upon nicotine in the posterior VTA.•Less dopaminergic-only neurons upon alcohol in the anterior VTA.•More glutamatergic neurons in the lateral anterior VTA. Initiation of use/co-use of nicotine and alcohol, commonly occurring in an episodic manner during adolescence, can imprint vulnerability to the developing brain and lead to addiction. The ventral tegmental area (VTA) is a key heterogeneous region of the mesocorticolimbic circuit involved in the binge-drinking and intoxication step of the addiction circuit. Higher human post-mortem VTA expression of vesicular glutamate transporter 2 (VGLUT2), a marker of the glutamatergic phenotype also expressed in dopaminergic [Tyrosine Hydroxylase (Th)-positive] neurons, has been associated with chronic nicotine use and co-use with alcohol. The present study aimed to map and characterize the Vglut2- and Th-expressing neurons in the VTA of adolescent male rats exposed or not to prolonged (six-weeks) episodic (three consecutive days/week) nicotine and/or alcohol administration. Nicotine (0.35 mg/kg free base) was injected subcutaneously, whereas alcohol (2 g/kg 20%) was administrated via gavage. Vglut2 and Th mRNA was assessed in the anterior and posterior VTA by use of in situ hybridization. The profile of neurons varied with substance-exposure among VTA subregions. Th-only expressing neurons were more abundant in the posterior VTA of the group exposed to nicotine-only, compared to controls. The same neurons were, on the contrary, less present in the anterior VTA of animals exposed to alcohol-only, who also displayed a higher number of Vglut2-expressing neurons in the lateral anterior VTA. VTA Vglut2- and Th-only neurons seem differentially involved in the effects of adolescent episodic nicotine and alcohol exposure in the anterior and posterior VTA.