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Further evidence for the involvement of the PPAR gamma system on alcohol intake and sensitivity in rodents
Linköping University, Department of Biomedical and Clinical Sciences, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences. Univ Camerino, Italy.ORCID iD: 0000-0001-5726-4814
Univ Camerino, Italy; Univ Gothenburg, Sweden.
Univ Camerino, Italy.
Addict Treatment Ctr, Italy.
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2020 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 237, p. 2983-2992Article in journal (Refereed) Published
Abstract [en]

Rationale Peroxisome Proliferator Activator receptors (PPARs) are intracellular receptors that function as transcription factors, which regulate specific metabolic and inflammatory processes. PPARs are broadly distributed in the body and are also expressed in the central nervous system, especially in areas involved in addiction-related behavioral responses. Recent studies support a role of PPARs in alcoholism and pioglitazone: a PPAR gamma agonist used for treatment of type 2 diabetes showed efficacy in reducing alcohol drinking, stress-induced relapse, and alcohol withdrawal syndrome in rats. Objectives and Methods In the current work, we tested the pharmacological effects of pioglitazone on binge-like alcohol consumption using an intermittent two-bottle choice paradigm in Wistar rats and on the "drinking in the dark" (DID) model in mice with selective deletion of PPAR gamma in neurons. Results Our data show that repeated administration of pioglitazone (10, 30 mg/kg) reduces high voluntary alcohol consumption in Wistar rats. Pre-treatment with the selective PPAR gamma antagonist GW9662 (5 mg/kg) completely prevented the effect of pioglitazone, demonstrating that its action is specifically mediated by activation of PPAR gamma. In line with this result, repeated administration of pioglitazone (30 mg/kg) attenuated binge alcohol consumption in PPAR gamma((+/+)) mice. Whereas in PPAR gamma((-/-)) mice, which exhibit reduced alcohol consumption, pioglitazone had no effect. Of note, PPAR gamma((-/-)) mice exhibited lower patterns of alcohol drinking without showing difference in sucrose (control) intake. Interestingly, PPAR gamma((-/-)) mice displayed a higher sensitivity to the sedative and ataxic effect of alcohol compared with their wild-type counterpart. Conclusions Collectively, these data suggest that PPAR gamma agonists, and specifically pioglitazone, could be potential therapeutics for the treatment of binge alcohol drinking.

Place, publisher, year, edition, pages
SPRINGER , 2020. Vol. 237, p. 2983-2992
Keywords [en]
PPAR gamma; Pioglitazone; Intermittent two-bottle choice; Drinking in the dark; Alcohol sensitivity
National Category
Substance Abuse
Identifiers
URN: urn:nbn:se:liu:diva-168511DOI: 10.1007/s00213-020-05586-wISI: 000549305300001PubMedID: 32676772OAI: oai:DiVA.org:liu-168511DiVA, id: diva2:1462220
Note

Funding Agencies|Italian Society of Pharmacology (SIF); grant PRIN 2017 [2017SXEXT5]; [NIH RO1 AA017447]; [NIH AA014351]

Available from: 2020-08-28 Created: 2020-08-28 Last updated: 2021-12-29

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