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.

Nicotine-seeking reinstatement is reduced by inhibition of instrumental memory reconsolidation

TEDESCO, Vincenzo;CHIAMULERA, Cristiano
2014-01-01

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.
nicotine; memory; NMDA receptors
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/869998
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