ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1668669
This article is part of the Research TopicPotential Therapeutic Targets in Alcohol Use Disorder: Insights from Recent Preclinical StudiesView all 4 articles
The involvement of GABA-rho receptors in regulating ethanol-induced elevation of dopamine, glycine and taurine within the nucleus accumbens of Wistar rats
Provisionally accepted
- 1Department of Pharmacology, University of Gothenburg, Gothenburg, Sweden
- 2Department of Psychiatry and Neurochemistry, University of Gothenburg, Gothenburg, Sweden
- 3Beroendekliniken, Sahlgrenska universitetssjukhuset, Gothenburg, Sweden
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Alcohol use disorder (AUD) causes significant morbidity and mortality globally. Ethanol's rewarding and reinforcing effects are attributed to activation of the mesolimbic dopamine system, increasing accumbal dopamine release. While activation of accumbal glycine receptors (GlyRs) is a prerequisite for ethanol-induced dopamine signaling, multiple transmitter systems may be involved; recent research implicates the GABA-rho receptor as a prominent target. Considering the structural and functional similarities between GlyRs and GABA-rho receptors, this study aimed to define the role of GlyRs and GABA-rho receptors in regulating baseline dopamine signalling and ethanol-induced elevation of extracellular dopamine and GlyR agonists, as well as to determine their involvement in the action of the ethanol relapse-preventing drug acamprosate. To investigate this, in vivo microdialysis was conducted in male Wistar rats. Local perfusion with either the GABA-rho receptor antagonist TPMPA or the GlyR antagonist strychnine prior to ethanol administration significantly reduced the ethanol-induced increase in dopamine levels. These findings suggest that both GlyRs and GABA-rho receptors are involved in mediating the dopamine-elevating effect of ethanol. In addition, a significant attenuation of the ethanol-induced glycine and taurine elevation was observed following both pretreatment with TPMPA and strychnine, whilst only GlyR blockade inhibited the acamprosate-induced increase of dopamine. Unlike strychnine, TPMPA alone did not alter dopamine levels, suggesting that GABA-rho receptors display features that distinguish them from GlyR. In conclusion, GABA-rho receptors regulate ethanol-induced dopamine and glycine/taurine levels within the nAc without affecting basal dopamine neurotransmission, suggesting their potential as a pharmacological target for the treatment of AUD.
Keywords: Dopamine, Ethanol, Taurine, GABA-rho, rat, Nucleus Accumbens, Glycine
Received: 18 Jul 2025; Accepted: 16 Oct 2025.
Copyright: © 2025 Cadeddu, Loftén, Ademar, Soderpalm, Adermark and Ericson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Mia Ericson, mia.ericson@neuro.gu.se
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