title: Incubation of extinction responding and cue-induced reinstatement, but not context- or drug priming-induced reinstatement, after withdrawal from methamphetamine.
abstract: In rats trained to self-administer methamphetamine, extinction responding in the presence of drug-associated contextual and discrete cues progressively increases after withdrawal (incubation of methamphetamine craving). The conditioning factors underlying this incubation are unknown. Here, we studied incubation of methamphetamine craving under different experimental conditions to identify factors contributing to this incubation. We also determined whether the rats' response to methamphetamine priming incubates after withdrawal. We trained rats to self-administer methamphetamine in a distinct context (context A) for 14 days (6 hours/day). Lever presses were paired with a discrete light cue. We then tested groups of rats in context A or a different non-drug context (context B) after 1 day, 1 week or 1 month for extinction responding with or without the discrete cue. Subsequently, we tested the rats for reinstatement of drug seeking induced by exposure to contextual, discrete cue, or drug priming (0, 0.25 and 0.5 mg/kg). Operant responding in the extinction sessions in contexts A or B was higher after 1 week and 1 month of withdrawal than after 1 day; this effect was context-independent. Independent of the withdrawal period, operant responding in the extinction sessions was higher when responding led to contingent delivery of the discrete cue. After extinction, discrete cue-induced reinstatement, but not context- or drug priming-induced reinstatement, progressively increased after withdrawal. Together, incubation of methamphetamine craving, as assessed in extinction tests, is primarily mediated by time-dependent increases in non-reinforced operant responding, and this effect is potentiated by exposure to discrete, but not contextual, cues.
authors.affiliation: Behavioral Neuroscience Research Branch, Intramural Research Program, NIDA, NIH, Baltimore, MD, USA.
authors.forename: Sweta
authors.initials: S
authors.lastname: Adhikary
authors.affiliation: Behavioral Neuroscience Research Branch, Intramural Research Program, NIDA, NIH, Baltimore, MD, USA.
authors.forename: Daniele
authors.initials: D
authors.lastname: Caprioli
authors.affiliation: Behavioral Neuroscience Research Branch, Intramural Research Program, NIDA, NIH, Baltimore, MD, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Venniro
authors.affiliation: Behavioral Neuroscience Research Branch, Intramural Research Program, NIDA, NIH, Baltimore, MD, USA.
authors.forename: Paige
authors.initials: P
authors.lastname: Kallenberger
authors.affiliation: Behavioral Neuroscience Research Branch, Intramural Research Program, NIDA, NIH, Baltimore, MD, USA.
authors.forename: Yavin
authors.initials: Y
authors.lastname: Shaham
authors.affiliation: Behavioral Neuroscience Research Branch, Intramural Research Program, NIDA, NIH, Baltimore, MD, USA.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bossert
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003216:Conditioning, Operant / Q000187:drug effects*; D066249:Craving / Q000187:drug effects*; D003463:Cues; D004195:Disease Models, Animal; D005108:Extinction, Psychological / Q000502:physiology*; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine
keywords: context; drug priming; extended access; extinction; incubation; reinstatement; relapse; self-administration