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Further evidence fo...
Further evidence for the involvement of the PPAR gamma system on alcohol intake and sensitivity in rodents
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- Domi, Esi (author)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten,Univ Camerino, Italy
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- Domi, Ana, 1990 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Univ Camerino, Italy; Univ Gothenburg, Sweden
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- Ubaldi, M. (author)
- Univ Camerino, Italy
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- Somaini, L. (author)
- Addict Treatment Ctr, Italy
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- Demopulos, G. (author)
- Omeros Corp, WA 98101 USA
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- Gaitanaris, G. (author)
- Omeros Corp, WA 98101 USA
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- Ciccocioppo, R. (author)
- Univ Camerino, Italy
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(creator_code:org_t)
- 2020-07-16
- 2020
- English.
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In: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 237, s. 2983-2992
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Beroendelära (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Substance Abuse (hsv//eng)
Keyword
- PPAR gamma
- Pioglitazone
- Intermittent two-bottle choice
- Drinking in
- the dark
- Alcohol sensitivity
- activated-receptor-gamma
- ethanol drinking
- intermittent access
- binge
- drinking
- consumption
- model
- neurobiology
- expression
- agonists
- mice
- Neurosciences & Neurology
- Pharmacology & Pharmacy
- Psychiatry
- PPAR gamma; Pioglitazone; Intermittent two-bottle choice; Drinking in the dark; Alcohol sensitivity
Publication and Content Type
- ref (subject category)
- art (subject category)
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