title: Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long-Evans rats by the α-2 adrenoreceptor antagonist yohimbine.
abstract: BACKGROUND
  Developing models to efficiently explore the mechanisms by which stress can mediate reinstatement of drug-seeking behavior is crucial to the development of new pharmacotherapies for alcohol use disorders.
  
  
  OBJECTIVE
  We examined the effects of multiple reinstatement sessions using the pharmacological stressor, yohimbine, in ethanol- and sucrose-seeking rats in order to develop a more efficient model of stress-induced reinstatement.
  
  
  METHODS
  Long-Evans rats were trained to self-administer 10% ethanol with a sucrose-fading procedure, 20% ethanol without a sucrose-fading procedure, or 5% sucrose in 30-min operant self-administration sessions, followed by extinction training. After reaching extinction criteria, the animals were tested once per week with yohimbine vehicle and yohimbine (2 mg/kg), respectively, 30 min prior to the reinstatement sessions or blood collection. Levels of reinstatement and plasma corticosterone (CORT) were determined each week for four consecutive weeks.
  
  
  RESULTS
  Yohimbine induced reinstatement of ethanol- and sucrose-seeking in each of the 4 weeks. Interestingly, the magnitude of the reinstatement decreased for the 10% ethanol group after the first reinstatement session but remained stable for the 20% ethanol group trained without sucrose. Plasma CORT levels in response to injection of both vehicle and yohimbine were significantly higher in the ethanol-trained animals compared to sucrose controls.
  
  
  CONCLUSIONS
  The stable reinstatement in the 20% ethanol group supports the use of this training procedure in studies using within-subject designs with multiple yohimbine reinstatement test sessions. Additionally, these results indicate that the hormonal response to stressors can be altered following extinction from self-administration of relatively modest amounts of ethanol.
authors.affiliation: Preclinical Development Group, Ernest Gallo Clinic and Research Center, 5858 Horton Street, Suite 200, Emeryville, CA, 94608, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Simms
authors.forename: Jemma K
authors.initials: JK
authors.lastname: Richards
authors.forename: Douglas
authors.initials: D
authors.lastname: Mill
authors.forename: Isabel
authors.initials: I
authors.lastname: Kanholm
authors.forename: Joan Y
authors.initials: JY
authors.lastname: Holgate
authors.forename: Selena E
authors.initials: SE
authors.lastname: Bartlett
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012008:Recurrence; D012055:Reinforcement Schedule; D012646:Self Administration; D013315:Stress, Psychological; D013395:Sucrose / Q000008:administration & dosage*; D015016:Yohimbine / Q000494:pharmacology*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D015016:Yohimbine; D000431:Ethanol; D013395:Sucrose; D003345:Corticosterone