title: Reward and relapse: complete gene-induced dissociation in an animal model of alcohol dependence.
abstract: BACKGROUND
  In animal models of continuous alcohol self-administration, in which physical dependence does not constitute the major factor of ethanol intake, 2 factors likely contribute to the perpetuation of alcohol self-administration: (i) the rewarding effects of ethanol and (ii) the contextual conditioning cues that exist along with the process of self-administration. Present studies are aimed at understanding the relative contribution of these factors on the perpetuation of heavy alcohol self-administration, as an indication of relapse.
  
  
  METHODS
  Wistar-derived UChB high ethanol drinker rats were allowed access to 10% ethanol and water on a 24-hour basis. In initial studies, an anticatalase shRNA gene-coding lentiviral vector aimed at inhibiting acetaldehyde generation was administered into the ventral tegmental area (VTA) of the animals prior to ethanol access. In subsequent studies, the lentiviral vector was administered to animals, which had consumed ethanol on a 24-hour basis, or a 1-hour basis, after the animals had reached high levels of ethanol intake for 60 to 80 days. In final studies, quinine (0.01%) was added to the ethanol solution to alter the conditioning taste/smell cues of alcohol that animals had chronically ingested.
  
  
  RESULTS
  Data indicate that the administration of an anticatalase vector into the VTA of naïve animals blocked reward and alcohol self-administration, while it was, nevertheless, inactive in inhibiting alcohol self-administration in rats that had been conditioned to ingest ethanol for over 2 months. The lack of inhibitory effect of the anticatalase vector on ethanol intake in animals that had chronically self-administered ethanol was fully reversed when the contextual conditioning cues of the alcohol solution were changed.
  
  
  CONCLUSIONS
  Data highlight the importance of conditioning factors in relapse and suggest that only abolishing or blunting it, along with long-lasting pharmacological treatment to reduce ethanol reward, may have protracted effects in reducing alcohol self-administration.
authors: Program of Molecular and Clinical Pharmacology, Faculty of Medicine, Institute of Biomedical Sciences, Santiago, Chile.
authors: María E
authors: ME
authors: Quintanilla
authors: Lutske
authors: L
authors: Tampier
authors: Eduardo
authors: E
authors: Karahanian
authors: Mario
authors: M
authors: Rivera-Meza
authors: Mario
authors: M
authors: Herrera-Marschitz
authors: Yedy
authors: Y
authors: Israel
mesh_terms: D000079:Acetaldehyde / Q000378:metabolism; D000428:Alcohol Drinking / Q000378:metabolism / Q000523:psychology* / Q000628:therapy; D000437:Alcoholism / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control* / Q000628:therapy*; D000818:Animals; D002374:Catalase / Q000037:antagonists & inhibitors / Q000235:genetics; D003463:Cues; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008845:Microinjections; D011803:Quinine / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D055502:Secondary Prevention; D012646:Self Administration; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D034741:RNA, Small Interfering; D000431:Ethanol; D011803:Quinine; D002374:Catalase; D000079:Acetaldehyde