title: Operant behavior and alcohol levels in blood and brain of alcohol-dependent rats.
abstract: BACKGROUND
  The purpose of the present investigation was to more clearly define blood-alcohol parameters associated with alcohol dependence produced by alcohol vapor inhalation and alcohol-containing liquid diet.
  
  
  METHODS
  Alcohol levels in blood and brain were compared during and after 4 hours of acute alcohol vapor exposure; also, brain-alcohol levels were assessed in alcohol-exposed (14-day alcohol vapor) and alcohol-naïve rats during and after 4 hours of acute alcohol vapor exposure. A separate group of rats were implanted with i.v. catheters, made dependent on alcohol via vapor inhalation, and tested for operant alcohol responding; blood-alcohol levels (BALs) were measured throughout operant alcohol drinking sessions during alcohol withdrawal. A final group of rats consumed an alcohol-liquid diet until they were dependent, and those rats were then tested for operant behavior at various withdrawal time points; BALs were measured at different withdrawal time points and after operant sessions.
  
  
  RESULTS
  Blood- and brain-alcohol levels responded similarly to vapor, but brain-alcohol levels peaked at a higher point and more slowly returned to zero in alcohol-naïve rats relative to alcohol-exposed rats. Alcohol vapor exposure also produced an upward shift in subsequent operant alcohol responding and resultant BALs. Rats consumed large quantities of alcohol-liquid diet, most of it during the dark cycle, sufficient to produce high blood-alcohol levels and elevated operant alcohol responding when tested during withdrawal from liquid diet.
  
  
  CONCLUSIONS
  These results emphasize that the key determinants of excessive alcohol drinking behavior are the BAL range and pattern of chronic high-dose alcohol exposure.
authors.affiliation: Committee on Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA. nickg@scripps.edu
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Gilpin
authors.forename: Amanda D
authors.initials: AD
authors.lastname: Smith
authors.forename: Maury
authors.initials: M
authors.lastname: Cole
authors.forename: Friedbert
authors.initials: F
authors.lastname: Weiss
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.forename: Heather N
authors.initials: HN
authors.lastname: Richardson
mesh_terms: D000280:Administration, Inhalation; D000437:Alcoholism / Q000378:metabolism* / Q000523:psychology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004032:Diet; D000431:Ethanol / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D017551:Microdialysis; D051381:Rats; D017208:Rats, Wistar; D012646:Self Administration
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol