title: Distinct patterns of neural activation associated with ethanol seeking: effects of naltrexone.
abstract: BACKGROUND
  Alcoholism, like other substance abuse disorders, is a chronically relapsing condition. Compared with other abused drugs, however, little is known about the neural mechanisms mediating ethanol (EtOH)-craving and -seeking behavior leading to relapse. This study, therefore, was conducted to identify candidate brain regions that are recruited by an EtOH-associated contextual stimulus (S(+)). A secondary objective was to determine whether EtOH S(+)-elicited neural recruitment patterns are modified by the opiate antagonist naltrexone (NTX), a compound that reduces cue-induced craving in alcoholics and attenuates ethanol seeking in animal models of relapse.
  
  
  METHODS
  Rats were tested in a conditioned reinstatement model of relapse with subsequent examination of brain c-fos expression patterns elicited by an EtOH S(+) versus a cue associated with nonreward (S(-)). In addition, modification of these expression patterns by NTX was examined.
  
  
  RESULTS
  The EtOH S(+) reinstated extinguished responding and increased c-fos expression within the prefrontal cortex, hippocampus, nucleus accumbens, and hypothalamic paraventricular nucleus (PVN). Naltrexone suppressed the S(+)-induced reinstatement and attenuated hippocampal CA3 c-fos expression, while increasing neural activity in the extended amygdala and PVN.
  
  
  CONCLUSIONS
  Ethanol-associated contextual stimuli recruit key brain regions that regulate associative learning, goal-directed behavior, and Pavlovian conditioning of emotional significance to previously neutral stimuli. In addition, the data implicate the hippocampus, amygdala, and PVN as potential substrates for the inhibitory effects of NTX on conditioned reinstatement.
authors.affiliation: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, California 92037, USA. cvdayas@scripps.edu
authors.forename: Christopher V
authors.initials: CV
authors.lastname: Dayas
authors.forename: Xiu
authors.initials: X
authors.lastname: Liu
authors.forename: Jeffery A
authors.initials: JA
authors.lastname: Simms
authors.forename: Friedbert
authors.initials: F
authors.lastname: Weiss
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000503:physiopathology; D000704:Analysis of Variance; D000818:Animals; D016739:Behavior, Addictive / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology*; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002492:Central Nervous System Depressants; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009271:Naltrexone / Q000627:therapeutic use*; D009292:Narcotic Antagonists / Q000627:therapeutic use*; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D009292:Narcotic Antagonists; D016761:Oncogene Proteins v-fos; D000431:Ethanol; D009271:Naltrexone