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Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats
National Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA.
National Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA.
Eli Lilly, Indianapolis, IN, USA.
National Institute on Alcohol Abuse and Alcoholism, NIH; Bethesda, MD, USA.
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2010 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 211, no 4, 367-375 p.Article in journal (Refereed) Published
Abstract [en]

RATIONALE: Melanin-concentrating hormone (MCH) is involved in regulation of appetitive behaviors as well as emotional reactivity and reward, behavioral domains relevant to alcohol addiction.

MATERIALS AND METHODS: We evaluated the effects of the non-peptide MCH1 receptor antagonist, GW803430 [6-(4-chloro-phenyl)-3-[3-methoxy-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one; 3-30 mg/kg, i.p.] on alcohol-related behaviors in Wistar rats.

RESULTS: Ex vivo binding experiments demonstrated that the GW803430 dose range used resulted in high central MCH1 receptor occupancy. Alcohol self-administration was dose-dependently and potently suppressed, by approximately 80% at the highest dose. Reinstatement of alcohol-seeking induced by alcohol-associated cues was essentially eliminated. In contrast, reinstatement induced by footshock stress was not significantly altered. Taste preference for a quinine/saccharin solution, locomotor activity, and alcohol elimination were unaffected.

CONCLUSION: Together, these observations support a specific involvement of the MCH system in mediating alcohol reward and cue-induced relapse to alcohol seeking. MCH1-R antagonism may constitute an attractive treatment target for alcohol use disorders.

Place, publisher, year, edition, pages
Springer, 2010. Vol. 211, no 4, 367-375 p.
Keyword [en]
Footshock, Reinstatement, Alcohol, Seeking, Saccharin, MCH1-R
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-101840DOI: 10.1007/s00213-010-1891-yPubMedID: 20628734OAI: oai:DiVA.org:liu-101840DiVA: diva2:666731
Available from: 2013-11-24 Created: 2013-11-24 Last updated: 2017-12-06Bibliographically approved

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Thorsell, AnnikaHeilig, Markus

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