Moderate ethanol drinking is sufficient to alter Ventral Tegmental Area dopamine neurons activity via functional and structural remodeling of GABAergic transmission. (1st February 2022)

• Record Type: Journal Article
• Authors: Ilari, A.; Curti, L.; Petrella, M.; Cannella, N.; La Rocca, A.; Ranieri, G.; Gerace, E.; Iezzi, D.; Silvestri, L.; Mannaioni, G.; Ciccocioppo, R.; Masi, A.
• Is Part Of: Neuropharmacology. Volume 203(2022)
• Publication Date: 2022-02-01
• Subjects: Voluntary alcohol drinking -- Ventral tegmental area -- Dopaminergic system -- GABAergic transmission -- Patch clamp; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108883
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Earlier studies have shown a major involvement of Ventral Tegmental Area (VTA) dopamine (DA) neurons in mediating the rewarding effects of ethanol (EtOH). Much less is known on the role of this system in mediating the transition from moderate to excessive drinking and abuse. Here we sought to explore the hypothesis that early stage drinking in rodents, resembling recreational EtOH use in humans, is sufficient to dysregulate VTA DA transmission thus increasing the propensity to use over time. To this purpose, midbrain slice recordings in mice previously exposed to an escalating (3, 6 and 12%) 18-day voluntary EtOH drinking paradigm was used. By recording from DA and γ-aminobutyric acid (GABA) VTA neurons in midbrain slices, we found that moderate EtOH drinking leads to a significant suppression of the spontaneous activity of VTA DA neurons, while increasing their response to acute EtOH application. We also found that chronic EtOH leads to the enhancement of GABA input frequency onto a subset of DA neurons. Structurally, chronic EtOH induced a significant increase in the number of GABA axonal boutons contacting DA neurons, suggesting deep rewiring of the GABA network. This scenario is consistent with a downmodulation of the reward DA system induced by moderate EtOH drinking, a neurochemical state defined as "hypodopaminergic" and previously associated with advanced stages of drug use in humans. In this context, increased sensitivity of DA neurons towards acute EtOH may represent the neurophysiological correlate of increased unitary rewarding value, possibly driving progression to addiction. Highlights: The basal firing activity of VTA DA neurons is depressed by moderate ethanol drinking. VTA glutamate transmission is not substantially affected. GABA transmission onto VTA DA neurons undergoes pre- and post-synaptic functional plasticity. The number of GABA synaptic contacts onto VTA DA neurons is significantly increased.