Cited by 177Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

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Baclofen Inhibits Heroin Self-Administration Behavior and Mesolimbic Dopamine Release

Xi, Zheng-Xiong, Stein, Elliot A.·1999·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1016/s0022-3565(24)35044-x

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Abstract

An emerging hypothesis to explain the mechanism of heroin-induced positive reinforcement states that opiates inhibit gamma-aminobutyric acid (GABA)-ergic interneurons within the mesocorticolimbic dopamine (DA) system to disinhibit DA neurons. In support of this hypothesis, we report that the development of heroin self-administration (SA) behavior in drug-naive rats and the maintenance of SA behavior in heroin-trained rats were both suppressed when the GABA(B) receptor agonist baclofen was coadministered with heroin. Microinjections of baclofen into the ventral tegmental area (VTA), but not the nucleus accumbens, decreased heroin reinforcement as indicated by a compensatory increase in SA behavior. Additionally, baclofen administered alone or along with heroin dose-dependently reduced heroin-induced DA release. This effect was blocked partially by intra-VTA infusion of the GABA(B) antagonist 2-hydroxysaclofen, suggesting an additional, perhaps GABA(A) receptor-mediated, disinhibitory effect. Taken together, these experiments, for the first time, demonstrate that heroin-reinforced SA behavior and nucleus accumbens DA release are mediated predominantly by GABA(B) receptors in the VTA and suggest that baclofen may be an effective agent in the treatment of opiate abuse.

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“Specifically, baclofen decreased the reinforcing effects of opioids in rat self-administration procedures (Xi and Stein, 1999; Ramshini et al., 2013), and abolished morphine preference in the place conditioning assay in mice (Meng et al.”
Background
Pharmacologie du baclofène et applications cliniques en addictologie
Imbert, B. (2016) · doi:10.70675/96dc9dcezae81z437ezb562z6e498be66a8f

Authors: Xi, Z.-X., & Stein, E. A.
Affiliations: Medical College of Wisconsin (US)
ORCID: Xi, Zheng-Xiong
Stein, Elliot A.
Venue: The Journal of Pharmacology and Experimental Therapeutics
Publisher: Elsevier BV
Published: 1999-09
Volume: 290
Issue: 3
Pages: 1369-1374
ISSN: 0022-3565 (ISSN-L)
DOI: 10.1016/s0022-3565(24)35044-x
OpenAlex: W2164726829
Cited by: 177
References: 40
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 7
FWCI: 4.34
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
PubMed (publishedVersion)
PubMed
Funders: National Institute on Drug Abuse (R01DA009465, DA 09465)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: baclofen, heroin self-administration, GABAB receptors, mesolimbic dopamine system, ventral tegmental area, nucleus accumbens, GABAergic interneurons, disinhibition, 2-hydroxysaclofen, GABAA receptor
MeSH terms: Animals, Baclofen, Behavior, Animal, Heroin, Dopamine, Electrodes, Limbic System, Male, Mesencephalon, Narcotic Antagonists, Narcotics, Nucleus Accumbens, Self Administration, Rats, Sprague-Dawley, Ventral Tegmental Area, GABA Agonists, Substance-Related Disorders, Rats

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Baclofen Inhibits Heroin Self-Administration Behavior and Mesolimbic Dopamine Release

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