title: Evidence that vasopressin V1b receptors mediate the transition to excessive drinking in ethanol-dependent rats.
abstract: Alcoholism is a devastating condition that represents a progression from initial alcohol use to dependence. Although most individuals are capable of consuming alcohol in a limited fashion, the development of alcohol dependence in a subset of individuals is often associated with negative emotional states (including anxiety and depression). Since the alleviation of this negative motivational state via excessive alcohol consumption often becomes a central goal of alcoholics, the transition from initial use to dependence is postulated to be associated with a transition from positive to negative reinforcement mechanisms. Vasopressin is a neuropeptide known to potentiate the effects of CRF on the HPA axis, and emerging evidence also suggests a role for centrally located vasopressin acting on V(1b) receptors in the regulation of stress- and anxiety-like behaviors in rodents. The present study determined state-dependent alterations in vasopressin/V(1b) R signaling in an animal model of ethanol dependence. The V(1b) R antagonist SSR149415 dose-dependently reduced excessive levels of ethanol self-administration observed in dependent animals without affecting the limited levels of ethanol drinking in non-dependent animals. Ethanol self-administration reduced V(1b) receptor levels in the basolateral amygdala of non-dependent animals, a neuroadaptation that could theoretically facilitate the positive reinforcing effects of alcohol. In contrast, V(1b) R levels were seemingly restored in ethanol-dependent rats, a switch that may in part underlie a transition from positive to negative reinforcement mechanisms with dependence. Together, our data suggest a key role for vasopressin/V(1b) R signaling in the transition to ethanol dependence.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA 92037, USA. edwards@scripps.edu
authors.forename: Scott
authors.initials: S
authors.lastname: Edwards
authors.forename: Miguel
authors.initials: M
authors.lastname: Guerrero
authors.forename: Ola M
authors.initials: OM
authors.lastname: Ghoneim
authors.forename: Edward
authors.initials: E
authors.lastname: Roberts
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
mesh_terms: D000428:Alcohol Drinking; D000437:Alcoholism; D000679:Amygdala / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D015153:Blotting, Western; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012646:Self Administration / Q000706:statistics & numerical data
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D002492:Central Nervous System Depressants; D000431:Ethanol