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

Maria Vrettou; Stefan Bernhard Thalhammer; Anne-Lie Svensson; Sylvie Dumas; Kent W Nilsson; Åsa Wallén-Mackenzie; Robert Fredriksson; Ingrid Nylander; Erika Comasco

doi:10.1016/j.dadr.2023.100180

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

Drug Alcohol Depend Rep. 2023 Jul 13:8:100180. doi: 10.1016/j.dadr.2023.100180. eCollection 2023 Sep.

Authors

Maria Vrettou¹, Stefan Bernhard Thalhammer¹, Anne-Lie Svensson², Sylvie Dumas³, Kent W Nilsson⁴, Åsa Wallén-Mackenzie⁵, Robert Fredriksson², Ingrid Nylander², Erika Comasco¹

Affiliations

¹ Department of Women's and Children's Health, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
² Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
³ Oramacell, Paris, France.
⁴ Centre for Clinical Research Västerås, Uppsala University, Västmanland County Hospital Västerås, Sweden.
⁵ Department of Organismal Biology, Uppsala University, Uppsala, Sweden.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Vglut2; alcohol; brain; expression; nicotine.