title: Involvement of arginine vasopressin and V1b receptor in alcohol drinking in Sardinian alcohol-preferring rats.
abstract: BACKGROUND
  Recent animal studies have shown that the level of stress-responsive arginine vasopressin (AVP) gene expression in the amygdala is increased during early withdrawal from long-term heroin or cocaine administration. The selective AVP V1b receptor antagonist SSR149415 (capable of exerting antidepressant-like and anxiolytic effects in animal models) also blocked stress-induced reinstatement of drug-seeking behavior. This study was undertaken to investigate the effects of alcohol and to determine whether (i) there are genetically determined differences in basal AVP mRNA levels in the medial/central amygdala (Me/CeA) and medial hypothalamus (MH) between selectively bred Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rats; (ii) the AVP mRNA levels are altered by long-term alcohol drinking in sP rats; and (iii) the V1b receptor antagonist SSR149415 alters alcohol drinking in sP rats.
  
  
  METHODS
  In Experiment 1, AVP mRNA levels were measured in the Me/CeA and MH of alcohol-naïve sP and sNP rats, and sP rats exposed to the standard, homecage 2-bottle "alcohol versus water" choice regimen 24 h/d for 17 days. In Experiment 2, SSR149415 (0, 3, 10, or 30 mg/kg; intraperitoneal) was acutely administered 30 minutes before lights off to alcohol-experienced sP rats. Alcohol, water, and food intake were monitored 6 and 24 hours later.
  
  
  RESULTS
  We found higher basal AVP mRNA levels in both Me/CeA and MH of alcohol-naïve sP than sNP rats; alcohol consumption decreased AVP mRNA levels in both brain regions of sP rats, suggesting genetically determined differences between the 2 rat lines and in the effects of alcohol drinking in sP rats. Acute treatment with SSR149415 significantly reduced alcohol intake of sP rats.
  
  
  CONCLUSIONS
  The stress-responsive AVP/V1b receptor system is 1 component of the neural circuitry underlying high alcohol drinking in sP rats.
authors.affiliation: Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York 10065, USA. yan.zhou@rockefeller.edu
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhou
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Colombo
authors.forename: Mauro A M
authors.initials: MA
authors.lastname: Carai
authors.forename: Ann
authors.initials: A
authors.lastname: Ho
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
authors.forename: Mary Jeanne
authors.initials: MJ
authors.lastname: Kreek
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics / Q000503:physiopathology*; D000679:Amygdala / Q000503:physiopathology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D007031:Hypothalamus / Q000503:physiopathology; D007211:Indoles / Q000494:pharmacology; D007558:Italy; D008297:Male; D011759:Pyrrolidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017483:Receptors, Vasopressin / Q000502:physiology*; D013997:Time Factors
chemical_list: C456029:1-(5-chloro-1-((2,4-dimethoxyphenyl)sulfonyl)-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl)-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide; D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D065092:Antidiuretic Hormone Receptor Antagonists; D002492:Central Nervous System Depressants; D007211:Indoles; D011759:Pyrrolidines; D012333:RNA, Messenger; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000431:Ethanol