title: Stimulation of voluntary ethanol intake by cannabinoid receptor agonists in ethanol-preferring sP rats.
abstract: BACKGROUND
  Recent studies have shown that the cannabinoid CB1 receptor antagonist, SR 141716, is capable of reducing voluntary ethanol intake in rodents, suggesting the involvement of the CB1 receptor in the neural circuitry mediating the positive reinforcing properties of ethanol.
  
  
  OBJECTIVE
  The present study extended to the agonists the investigation on the pharmacological manipulation of ethanol intake by cannabinoid agents.
  
  
  METHODS
  Selectively bred, Sardinian alcohol-preferring (sP) rats were offered ethanol and water under the two-bottle free choice procedure with unlimited access for 24 h/day.
  
  
  RESULTS
  The acute administration of WIN 55,212-2 (0.5-2 mg/kg; IP) and CP 55,940 (3-30 microg/kg; IP) induced a significant, dose-dependent increase in ethanol intake. Conversely, water consumption and intake of regular food and a highly palatable sucrose solution were not affected by treatment with WIN 55,212-2 and CP 55,940. The stimulatory effect of WIN 55,212-2 and CP 55,940 on ethanol intake was completely prevented by administration of SR 141716 (0.3 mg/kg; IP) and the opioid receptor antagonist, naloxone (0.1 mg/kg; IP).
  
  
  CONCLUSIONS
  Administration of WIN 55,212-2 and CP 55,940 promoted voluntary ethanol intake in sP rats. This effect was mediated by stimulation of the cannabinoid CB1 receptor and required the activation of the endogenous opioid system. The results of the present study add further support to the hypothesis that the cannabinoid CB1 receptor is part of the neural substrate regulating ethanol intake. These results are also discussed in terms of WIN 55,212-2 and CP 55,940 administration possibly fixing to a higher level the hedonic set-point mechanism regulating ethanol drinking behavior in sP rats.
authors.affiliation: CNR Institute of Neurogenetics and Neuropharmacology, c/o Department of Neuroscience, University of Cagliari, S.S. 554, Km 4.5, I-09042, Monserrato (CA), Italy. colomb@unica.it
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Colombo
authors.forename: Salvatore
authors.initials: S
authors.lastname: Serra
authors.forename: Giuliana
authors.initials: G
authors.lastname: Brunetti
authors.forename: Raquel
authors.initials: R
authors.lastname: Gomez
authors.forename: Samuele
authors.initials: S
authors.lastname: Melis
authors.forename: Giovanni
authors.initials: G
authors.lastname: Vacca
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Carai
authors.forename: Luigi
authors.initials: L
authors.lastname: Gessa
mesh_terms: D000284:Administration, Oral; D000428:Alcohol Drinking / Q000235:genetics; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D048588:Benzoxazines; D003511:Cyclohexanols / Q000494:pharmacology; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D051381:Rats; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D000700:Analgesics; D048588:Benzoxazines; D003511:Cyclohexanols; D009025:Morpholines; D009281:Naphthalenes; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013395:Sucrose; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; C054649:3-(2-hydroxy-4-(1,1-dimethylheptyl)phenyl)-4-(3-hydroxypropyl)cyclohexanol