Suppression of alcohol self-administration and reinstatement of alcohol seeking by melanin-concentrating hormone receptor 1 (MCH1-R) antagonism in Wistar rats.
Psychopharmacology (Berl)
; 211(4): 367-75, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20628734
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirimidinonas
/
Tiofenos
/
Consumo de Bebidas Alcoólicas
/
Receptores de Somatostatina
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article