title: Nicotine-seeking reinstatement is reduced by inhibition of instrumental memory reconsolidation.
abstract: The reinforcing properties of nicotine play a major role in instrumental conditioning to nicotine taking in smokers. Retrieval of nicotine-related memories may promote relapse to nicotine seeking after prolonged abstinence. Once consolidated, memories are stable, but they return to a labile phase, called reconsolidation, after their retrieval. The aim of our study was to investigate whether it was possible to interfere with the reconsolidation of instrumental nicotine-related memories by acting at glutamatergic receptors [N-methyl-D-aspartate receptors (NMDARs)] to prevent relapse to nicotine-seeking behaviour in the rat. We assessed whether the NMDAR antagonist MK-801, administered before or after nicotine-related instrumental memory retrieval, can reduce reinstatement of nicotine-seeking behaviour in rats previously trained to nicotine self-administration. Following a period of forced abstinence, MK-801 (0.1 mg/kg intraperitoneally) was administered 30 min before or 1 h after the re-exposure to 20 lever presses without any contingency in the training context to retrieve instrumental memory. MK-801 administered after, but not before, retrieval inhibited reinstatement compared with vehicle controls and groups without retrieval of instrumental memory. Interestingly, a retrieval factor effect was observed as an increase of reinstatement in vehicle-treated groups, suggesting a behavioural outcome of the occurrence of instrumental memory reconsolidation. Our findings suggest that, by acting on NMDARs, it is possible to reduce the reinstatement of nicotine-seeking behaviour through inhibition of instrumental nicotine-related memory reconsolidation.
authors.affiliation: Department of Public Health & Community Medicine, University of Verona, Verona, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tedesco
authors.forename: Anna
authors.initials: A
authors.lastname: Mutti
authors.forename: Alessia
authors.initials: A
authors.lastname: Auber
authors.forename: Cristiano
authors.initials: C
authors.lastname: Chiamulera
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018722:Nicotinic Agonists; D016291:Dizocilpine Maleate; D009538:Nicotine