Evidence map›Paper›PMID 42768774›Full record

ArticleAlcohol, clinical & experimental research2026

A Role for Glycine Transporter-2 Inhibitors in Regulating Accumbal Dopamine Levels and Voluntary Alcohol Intake in Rats.

Yasmin Olsson, Klara Danielsson, Ana Domi, Helga Lidö, Linda Engström Ruud, Mia Ericson, Bo Söderpalm

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Article in Alcohol, clinical & experimental research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Yasmin OlssonBeroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden.ORCID https://orcid.org/0000-0003-4547-3584
Klara DanielssonAddiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Ana DomiAddiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID https://orcid.org/0000-0003-2796-2333
Helga LidöBeroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden.
Linda Engström RuudDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Mia EricsonAddiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.ORCID https://orcid.org/0000-0002-7557-7109
Bo SöderpalmBeroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden.ORCID https://orcid.org/0000-0001-9434-6878

Funding

Göteborgs Läkaresällskap GLS-999159Grants from the Swedish State under the agreement between the Swedish Government and county council Region Västra Götaland, the ALF agreement ALFGBG-984234Stiftelsen Lars Hiertas MinneStiftelsen Professor Bror Gadelius MinnesfondStiftelserna Wilhelm och Martina Lundgrens 2024-SA-4436
6 · The paper itself

Abstract

backgroundGlycinergic neurotransmission has been suggested as a tentative pharmacological treatment target for Alcohol Use Disorder (AUD), a devastating brain disease with limited treatment options that involves reduced dopamine (DA) activity in the nucleus Accumbens (nAc) and loss of control of alcohol intake. Glycine receptors (GlyRs) in the nAc, a pivotal part of the brain reward circuitry, are involved in regulating basal and alcohol-induced accumbal DA levels as well as voluntary alcohol intake in rats.

methodsThis study in rats examined if inhibition of the glycine transporter 2 (GlyT-2, SLC6A5), present within glycinergic synapses, alters (1) accumbal DA and glycine content as measured by in vivo microdialysis coupled to HPLC and (2) the alcohol deprivation effect (ADE) in a two-bottle-choice alcohol consumption paradigm. Finally, (3) the presence of GlyT2-expressing fibers and GlyRs in the nAc was examined by immunohistochemistry (IHC).

resultsIn brief, the two partial GlyT2-inhibitors N-Arachidonyl-Glycine (NAGly, 10 mg/kg i.p.) and Opiranserin (20 mg/kg i.p.), but not the full GlyT2-inhibitor Org 25543, slightly elevated accumbal DA levels, while no effects on extrasynaptic glycine levels were observed. The reversible GlyT1-inhibitor Bitopertin (10 mg/kg p.o.) produced a pronounced glycine and DA elevation but combined GlyT1- and GlyT2 inhibition did not yield any statistically significant additive effects. In the alcohol consumption study, NAGly abolished the ADE as compared to placebo treatment. Finally, histology confirmed the presence of GlyT2 and GlyR in the nAc, although with a higher signal for GlyT2 in, for example, septal and basal forebrain regions.

conclusionsOverall, this study indicates that synaptic GlyRs are involved in regulating nAc DA levels and alcohol intake in rats, but probably to a lesser extent than extrasynaptic GlyRs. Further studies that specifically target GlyT2 in, for example, the nAc and septal regions and that utilize refined techniques for measuring synaptic glycine levels are warranted to better characterize the role of glycinergic innervation in the reward circuitry and for regulating alcohol intake.

Indexed as

Alcohol DrinkingDopamineGlycine Plasma Membrane Transport ProteinsNucleus AccumbensAnimalsEthanolGlycineMaleMicrodialysisPiperidinesRatsTetrahydronaphthalenesDopamineEthanolGlycineGlycine Plasma Membrane Transport ProteinsPiperidinesSlc6a5 protein, ratTetrahydronaphthalenesalcohol addictiondopamineethanol consumptionglycine transporternucleus Accumbens

Identifiers

PMID42768774
PMCPMC13594685

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.