title: Effect of prazosin and guanfacine on stress-induced reinstatement of alcohol and food seeking in rats.
abstract: OBJECTIVE
  Relapse to alcohol use during abstinence or maladaptive eating habits during dieting is often provoked by stress. The anxiogenic drug yohimbine, which causes stress-like responses in humans and non-humans, reliably reinstates alcohol and food seeking in a rat relapse model. Yohimibine is a prototypical alpha-2 adrenoceptor antagonist, but results from studies on noradrenaline's role in yohimbine-induced reinstatement of drug and food seeking are inconclusive. Here, we further addressed this issue by studying the effect of the alpha-1 adrenoceptor antagonist prazosin and the alpha-2 adrenoceptor agonist guanfacine on yohimbine-induced reinstatement.
  
  
  METHODS
  In exp. 1, we trained rats to self-administer alcohol (12% w/v, 1 h/day), and after extinction of alcohol-reinforced lever pressing, we tested prazosin's (0.5, 1.0, and 2.0 mg/kg, i.p.) or guanfacine's (0.125, 0.25, and 0.5 mg/kg, i.p.) effect on yohimbine (1.25 mg/kg, i.p.)-induced reinstatement; we also examined prazosin's effect on intermittent-footshock-stress-induced reinstatement. In exp. 2, we trained food-restricted rats to self-administer 45 mg food pellets and first examined prazosin's or guanfacine's effects on food-reinforced responding, and then, after extinction of lever presses, on yohimbine-induced reinstatement.
  
  
  RESULTS
  Prazosin (0.5-2.0 mg/kg) blocked yohimbine-induced reinstatement of food and alcohol seeking, as well as footshock-induced reinstatement of alcohol seeking. Guanfacine attenuated yohimbine-induced reinstatement of alcohol seeking at the highest dose (0.5 mg/kg), but its effect on yohimbine-induced reinstatement of food seeking was not significant. Neither prazosin nor guanfacine affected high-rate food-reinforced responding.
  
  
  CONCLUSIONS
  Results demonstrate an important role of postsynaptic alpha-1 adrenoceptors in stress-induced reinstatement of alcohol and food seeking.
authors.affiliation: Neurobiology of Alcohol Laboratory, Centre for Addiction and Mental Health, 33 Russell Street, Toronto, ON M5S 2S1, Canada. Anh_le@camh.net
authors.forename: A D
authors.initials: AD
authors.lastname: Lê
authors.forename: Douglas
authors.initials: D
authors.lastname: Funk
authors.forename: Walter
authors.initials: W
authors.lastname: Juzytsch
authors.forename: Kathleen
authors.initials: K
authors.lastname: Coen
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Navarre
authors.forename: Carlo
authors.initials: C
authors.lastname: Cifani
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage*; D005247:Feeding Behavior / Q000187:drug effects*; D016316:Guanfacine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D011224:Prazosin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D055502:Secondary Prevention; D012646:Self Administration; D013315:Stress, Psychological; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D015016:Yohimbine; D016316:Guanfacine; D000431:Ethanol; D011224:Prazosin