The Effect of Postretrieval Extinction of Nicotine Pavlovian Memories in Rats Trained to Self-Administer Nicotine

Retrieval (reactivation) of smoking-related memories is a potent trigger of relapse among ex-smokers, and manipulation of smoking-related memories is considered to be a promising target for therapeutic intervention. Recent studies have shown that postreactivation extinction attenuates drug-related memories and relapse to drug-seeking both in rodents and in humans. We investigated the effect of postreactivation extinction in a rat model of relapse to nicotine-seeking. Rats were trained to self-administer nicotine in context A (CxA). Pressing the active lever resulted in the nicotine infusion paired with a cue-light (CS). Nicotine-related Pavlovian memories were then reactivated via presentation of 3 non-contingent CS. We then extinguished nicotine-related memories in a distinct context (CxB) followed 24hr later by the assessment of renewal of responding in CxA. Postreactivation extinction, applied 1 but not 6hr after reactivation, induced a significant reduction of the rate of responding on renewal compared to responding during nicotine self-administration, whereas no such effect of CS-Extinction was observed in No-Reactivation group. However, between-group comparisons of responding during renewal did not show any significant difference. Current results show that the reactivation of nicotine-related Pavlovian memories may reduce the effect of renewal to exert nicotine-seeking. However, it appears that this effect is small in size and is not significantly different from CS-Extinction alone.