The melanin-concentrating hormone-1 receptor modulates alcohol-induced reward and DARPP-32 phosphorylation.
Psychopharmacology (Berl)
; 233(12): 2355-63, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-27044354
ABSTRACT
RATIONALE Melanin-concentrating hormone (MCH) is involved in the regulation of food intake and has recently been associated with alcohol-related behaviors. Blockade of MCH-1 receptors (MCH1-Rs) attenuates operant alcohol self-administration and decreases cue-induced reinstatement, but the mechanism through which the MCH1-R influences these behaviors remains unknown. MCH1-Rs are highly expressed in the nucleus accumbens shell (NAcSh) where they are co-expressed with dopamine (DA) receptors. MCH has been shown to potentiate responses to dopamine and to increase phosphorylation of DARPP-32, an intracellular marker of DA receptor activation, in the NAcSh. METHODS:
In the present study, we investigated the role of the MCH1-R in alcohol reward using the conditioned place preference (CPP) paradigm. We then used immunohistochemistry (IHC) to assess activation of downstream signaling after administration of a rewarding dose of alcohol.RESULTS:
We found that alcohol-induced CPP was markedly decreased in mice with a genetic deletion of the MCH1-R as well as after pharmacological treatment with an MCH1-R antagonist, GW803430. In contrast, an isocaloric dose of dextrose did not produce CPP. The increase in DARPP-32 phosphorylation seen in wildtype (WT) mice after acute alcohol administration in the NAcSh was markedly reduced in MCH1-R knock-out (KO) mice.CONCLUSION:
Our results suggest that MCH1-Rs regulate the rewarding properties of alcohol through interactions with signaling cascades downstream of DA receptors in the NAcSh.Palavras-chave
Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recompensa
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Receptores de Somatostatina
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Condicionamento Psicológico
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Etanol
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Fosfoproteína 32 Regulada por cAMP e Dopamina
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Núcleo Accumbens
Limite:
Animals
Idioma:
En
Revista:
Psychopharmacology (Berl)
Ano de publicação:
2016
Tipo de documento:
Article