title: Pavlovian-conditioned alcohol-seeking behavior in rats is invigorated by the interaction between discrete and contextual alcohol cues: implications for relapse.
abstract: BACKGROUND
  Drug craving can be independently stimulated by cues that are directly associated with drug intake (discrete drug cues), as well as by environmental contexts in which drug use occurs (contextual drug cues). We tested the hypothesis that the context in which a discrete alcohol-predictive cue is experienced can influence how robustly that cue stimulates alcohol-seeking behavior.
  
  
  METHODS
  Male, Long-Evans rats received Pavlovian discrimination training (PDT) sessions in which one conditioned stimulus (CS+; 16 trials/session) was paired with ethanol (0.2 mL/CS+) and a second stimulus (CS-; 16 trials/session) was not. PDT occurred in a specific context, and entries into a fluid port where ethanol was delivered were measured during each CS. Next, rats were acclimated to an alternate (nonalcohol) context where cues and ethanol were withheld. Responses to the nonextinguished CS+ and CS- were then tested without ethanol in the alcohol-associated PDT context, the nonalcohol context or a third, novel context.
  
  
  RESULTS
  Across PDT the CS+ elicited more port entries than the CS-, indicative of Pavlovian discrimination learning. At test, the CS+ elicited more port entries than the CS- in all three contexts: however, alcohol seeking driven by the CS+ was more robust in the alcohol-associated context. In a separate experiment, extinguishing the context-alcohol association did not influence subsequent CS+ responding but reduced alcohol seeking during non-CS+ intervals during a spontaneous recovery test.
  
  
  CONCLUSIONS
  These results indicate that alcohol-seeking behavior driven by a discrete Pavlovian alcohol cue is strongly invigorated by an alcohol context, and suggest that contexts may function as excitatory Pavlovian conditioned stimuli that directly trigger alcohol-seeking behavior.
authors.affiliation: Center for Studies in Behavioural Neurobiology/Groupe de recherche en neurobiologie comportementale, Department of Psychology, Concordia University Montreal, Quebec, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: Remedios
authors.affiliation: Center for Neural Science, New York University New York, New York.
authors.forename: Catherine
authors.initials: C
authors.lastname: Woods
authors.affiliation: Center for Studies in Behavioural Neurobiology/Groupe de recherche en neurobiologie comportementale, Department of Psychology, Concordia University Montreal, Quebec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Tardif
authors.affiliation: Ernest Gallo Clinic & Research Center, University of California at San Francisco Emeryville, California ; Department of Neurology, University of California San Francisco, California ; Wheeler Center for the Neurobiology of Addiction, University of California at San Francisco San Francisco, California.
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Janak
authors.affiliation: Center for Studies in Behavioural Neurobiology/Groupe de recherche en neurobiologie comportementale, Department of Psychology, Concordia University Montreal, Quebec, Canada.
authors.forename: Nadia
authors.initials: N
authors.lastname: Chaudhri
mesh_terms: D000437:Alcoholism / Q000503:physiopathology*; D000818:Animals; D003214:Conditioning, Classical; D003463:Cues; D004192:Discrimination, Psychological; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D012008:Recurrence
chemical_list: D000431:Ethanol
keywords: Alcoholism; Pavlovian-conditioning; context; ethanol; learning; reinstatement; renewal