{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T06:28:00Z","timestamp":1761632880167,"version":"build-2065373602"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T00:00:00Z","timestamp":1761609600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Alcohol use disorder (AUD) causes significant morbidity and mortality globally. Ethanol\u2019s 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      To investigate this,\n                      <jats:italic>in vivo<\/jats:italic>\n                      microdialysis was conducted in male Wistar rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1668669","type":"journal-article","created":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T06:23:55Z","timestamp":1761632635000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The involvement of GABA-rho receptors in regulating ethanol-induced elevation of dopamine, glycine and taurine within the nucleus accumbens of Wistar rats"],"prefix":"10.3389","volume":"16","author":[{"given":"Davide","family":"Cadeddu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Loft\u00e9n","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Ademar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bo","family":"S\u00f6derpalm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Louise","family":"Adermark","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mia","family":"Ericson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1016\/j.neuron.2017.10.032","article-title":"Alcohol and the brain: neuronal molecular targets, synapses, and circuits","volume":"96","author":"Abrahao","year":"2017","journal-title":"Neuron"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e13224","DOI":"10.1111\/adb.13224","article-title":"Sodium acamprosate and calcium exert additive effects on nucleus accumbens dopamine in the rat","volume":"27","author":"Ademar","year":"2022","journal-title":"Addict. Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"17863","DOI":"10.1038\/s41598-023-45167-3","article-title":"Acamprosate reduces ethanol intake in the rat by a combined action of different drug components","volume":"13","author":"Ademar","year":"2023","journal-title":"Sci. Rep."},{"key":"B4","doi-asserted-by":"publisher","first-page":"810","DOI":"10.1097\/00000374-199806000-00006","article-title":"Mechanism of action of acamprosate. Part II. Ethanol dependence modifies effects of acamprosate on NMDA receptor binding in membranes from rat cerebral cortex","volume":"22","author":"Al Qatari","year":"1998","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1038\/s41593-021-00898-2","article-title":"Ventral tegmental area GABAergic inhibition of cholinergic interneurons in the ventral nucleus accumbens shell promotes reward reinforcement","volume":"24","author":"Al-Hasani","year":"2021","journal-title":"Nat. Neurosci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1234","DOI":"10.1152\/jn.1995.73.3.1234","article-title":"Temporal and spatial characteristics of tonically active neurons of the primate's striatum","volume":"73","author":"Aosaki","year":"1995","journal-title":"J. Neurophysiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"e85525","DOI":"10.1371\/journal.pone.0085525","article-title":"GABAA receptors containing \u03c11 subunits contribute to in vivo effects of ethanol in mice","volume":"9","author":"Blednov","year":"2014","journal-title":"PLoS One"},{"key":"B8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/s0165-6147(99)01413-3","article-title":"The 'ABC' of GABA receptors","volume":"21","author":"Bormann","year":"2000","journal-title":"Trends Pharmacol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"ENEURO.0397","DOI":"10.1523\/ENEURO.0397-17.2018","article-title":"Targeted activation of cholinergic interneurons accounts for the modulation of dopamine by striatal nicotinic receptors","volume":"5","author":"Brimblecombe","year":"2018","journal-title":"eNeuro"},{"key":"B10","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1038\/nature11657","article-title":"Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning","volume":"492","author":"Brown","year":"2012","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.celrep.2012.05.011","article-title":"Selective activation of cholinergic interneurons enhances accumbal phasic dopamine release: setting the tone for reward processing","volume":"2","author":"Cachope","year":"2012","journal-title":"Cell Rep."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1097\/00001756-199505300-00011","article-title":"Activation of GABA rho 1 receptors by glycine and beta-alanine","volume":"6","author":"Calvo","year":"1995","journal-title":"Neuroreport"},{"key":"B13","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1007\/s00210-002-0674-3","article-title":"Local acamprosate modulates dopamine release in the rat nucleus accumbens through NMDA receptors: an in vivo microdialysis study","volume":"367","author":"Cano-Cebrian","year":"2003","journal-title":"Naunyn Schmiedeb. Arch. Pharmacol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/j.1530-0277.2009.01062.x","article-title":"Glycine receptors involved in acamprosate's modulation of accumbal dopamine levels: an in vivo microdialysis study","volume":"34","author":"Chau","year":"","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1111\/j.1530-0277.2009.01063.x","article-title":"Glycine receptors in the nucleus accumbens involved in the ethanol intake-reducing effect of acamprosate","volume":"34","author":"Chau","year":"","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B16","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.pbb.2018.09.009","article-title":"Acamprosate's ethanol intake-reducing effect is associated with its ability to increase dopamine","volume":"175","author":"Chau","year":"2018","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B17","doi-asserted-by":"publisher","first-page":"498","DOI":"10.1093\/alcalc\/agu047","article-title":"Increase in nucleus accumbens dopamine levels following local ethanol administration is not mediated by acetaldehyde","volume":"49","author":"Clarke","year":"2014","journal-title":"Alcohol Alcohol"},{"key":"B18","first-page":"108","article-title":"Alcohol and dopamine","volume":"21","author":"Di Chiara","year":"1997","journal-title":"Alcohol Health Res. World"},{"key":"B19","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1016\/s0014-2999(98)00602-5","article-title":"Voluntary ethanol intake in the rat and the associated accumbal dopamine overflow are blocked by ventral tegmental mecamylamine","volume":"358","author":"Ericson","year":"1998","journal-title":"Eur. J. Pharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1111\/j.1369-1600.2010.00245.x","article-title":"Rising taurine and ethanol concentrations in nucleus accumbens interact to produce dopamine release after ethanol administration","volume":"16","author":"Ericson","year":"2011","journal-title":"Addict. Biol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e12761","DOI":"10.1111\/adb.12761","article-title":"Different dopamine tone in ethanol high- and low-consuming wistar rats","volume":"25","author":"Ericson","year":"2020","journal-title":"Addict. Biol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/s0022-3565(25)23929-5","article-title":"Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol","volume":"239","author":"Imperato","year":"1986","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.neuropharm.2014.03.010","article-title":"The involvement of accumbal glycine receptors in the dopamine-elevating effects of addictive drugs","volume":"82","author":"Jonsson","year":"2014","journal-title":"Neuropharmacology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e12959","DOI":"10.1111\/adb.12959","article-title":"An acetylcholine-dopamine interaction in the nucleus accumbens and its involvement in ethanol's dopamine-releasing effect","volume":"26","author":"Loft\u00e9n","year":"2021","journal-title":"Addict. Biol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e13349","DOI":"10.1111\/adb.13349","article-title":"Regulation of ethanol-mediated dopamine elevation by glycine receptors located on cholinergic interneurons in the nucleus accumbens","volume":"28","author":"Loft\u00e9n","year":"2023","journal-title":"Addict. Biol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1051","DOI":"10.1007\/s00702-025-02928-w","article-title":"Alcohol-induced accumbal dopamine- and taurine release in female and male Wistar rats, an in vivo microdialysis study","volume":"132","author":"Loft\u00e9n","year":"2025","journal-title":"J. Neural Transm. (Vienna)"},{"key":"B27","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1080\/08990220.2017.1317240","article-title":"Effect of TPMPA (GABA(C) receptor antagonist) on neuronal response properties in rat barrel cortex","volume":"34","author":"Mohammadi","year":"2017","journal-title":"Somatosens. Mot. Res."},{"key":"B28","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1097\/01.alc.0000150006.17168.f7","article-title":"Glycine receptors regulate dopamine release in the rat nucleus accumbens","volume":"29","author":"Molander","year":"","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1097\/01.alc.0000150012.09608.81","article-title":"Accumbal strychnine-sensitive glycine receptors: an access point for ethanol to the brain reward system","volume":"29","author":"Molander","year":"","journal-title":"Alcohol Clin. Exp. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1881","DOI":"10.1111\/bph.13768","article-title":"GABA-\u03c1 receptors: distinctive functions and molecular pharmacology","volume":"174","author":"Naffaa","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.neures.2008.03.009","article-title":"Modulation of human GABArho1 receptors by taurine","volume":"61","author":"Ochoa-de la Paz","year":"2008","journal-title":"Neurosci. Res."},{"key":"B32","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/s0014-2999(02)01272-4","article-title":"Effects of acute acamprosate and homotaurine on ethanol intake and ethanolstimulated mesolimbic dopamine release","volume":"437","author":"Olive","year":"2002","journal-title":"Eur. J. Pharmacol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/0306-4522(94)00399-p","article-title":"Comparison of the actions of glycine and related amino acids on isolated third order neurons from the tiger salamander retina","volume":"64","author":"Pan","year":"1995","journal-title":"Neuroscience"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1016\/s0306-4522(01)00130-0","article-title":"Expression and function of glycine receptors in striatal cholinergic interneurons from rat and mouse","volume":"104","author":"Sergeeva","year":"2001","journal-title":"Neuroscience"},{"key":"B35","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1007\/7854_2011_170","article-title":"Neurocircuitry involved in the development of alcohol addiction: the dopamine system and its access points","volume":"13","author":"S\u00f6derpalm","year":"2013","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"B36","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/npp.2013.264","article-title":"Acamprosate produces its anti-relapse effects via calcium","volume":"39","author":"Spanagel","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"B37","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.neuron.2012.04.038","article-title":"Striatal dopamine release is triggered by synchronized activity in cholinergic interneurons","volume":"75","author":"Threlfell","year":"2012","journal-title":"Neuron"},{"key":"B38","doi-asserted-by":"publisher","first-page":"172831","DOI":"10.1016\/j.pbb.2019.172831","article-title":"Sub-chronic taurine administration induces behavioral sensitization but does not influence ethanol-induced dopamine release in the nucleus accumbens","volume":"188","author":"Ulenius","year":"2020","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3113","DOI":"10.1007\/s12035-023-03263-5","article-title":"Role of \u03b16-Nicotinic receptors in alcohol-induced GABAergic synaptic transmission and plasticity to cholinergic interneurons in the nucleus accumbens","volume":"60","author":"Wadsworth","year":"2023","journal-title":"Mol. Neurobiol."},{"volume-title":"Global status report on alcohol and health 2018","year":"2018","key":"B40"},{"key":"B41","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1016\/s0026-895x(25)13444-5","article-title":"Characterization of bicuculline\/baclofen-insensitive (rho-like) gamma-aminobutyric acid receptors expressed in Xenopus oocytes. II. Pharmacology of gamma-aminobutyric acidA and gamma-aminobutyric acidB receptor agonists and antagonists","volume":"43","author":"Woodward","year":"1993","journal-title":"Mol. Pharmacol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"e13108","DOI":"10.1111\/adb.13108","article-title":"Modulation of dopamine release by ethanol is mediated by atypical GABA(A) receptors on cholinergic interneurons in the nucleus accumbens","volume":"27","author":"Yorgason","year":"2022","journal-title":"Addict. Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/s0165-6147(00)01625-4","article-title":"Structure and function of GABA(C) receptors: a comparison of native versus recombinant receptors","volume":"22","author":"Zhang","year":"2001","journal-title":"Trends Pharmacol. Sci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1038\/nn769","article-title":"Endogenous nicotinic cholinergic activity regulates dopamine release in the striatum","volume":"4","author":"Zhou","year":"2001","journal-title":"Nat. Neurosci."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1668669\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T06:23:56Z","timestamp":1761632636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1668669\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,28]]},"references-count":44,"alternative-id":["10.3389\/fphar.2025.1668669"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1668669","relation":{},"ISSN":["1663-9812"],"issn-type":[{"type":"electronic","value":"1663-9812"}],"subject":[],"published":{"date-parts":[[2025,10,28]]},"article-number":"1668669"}}