Extinction applied after retrieval of nicotine pavlovian memories reduces renewal of nicotine seeking behavior in rats.

Retrieval of previously consolidated memories, including drug-associated memories, induces a labile phase during which these memories could be disrupted or reconsolidated. This is an opportunity for selective disruption of those drug-memories that induce relapse to drug-seeking. Aim of our project is to investigate if it is possible to disrupt nicotine-memories reconsolidation by associating Pavlovian extinction to retrieval, as recently shown for fear-memory reconsolidation (Monfils et al, 2009). We tested the effects of Pavlovian extinction applied after retrieval of nicotine-cues, on renewal of nicotine-seeking in rats trained to nicotine self-administration (S/A). Sixty male Sprague-Dawley rats were trained to a nicotine S/A schedule (FR1: 0.3 mg/kg/infusion IV nicotine + 5-s cue lamp (CS), 1-h session), followed by a period of instrumental between-session extinction. Then, rats were divided into two groups exposed to Retrieval (3 no-contingent CS presentations) or not (NoRetrieval) in a new context (CxB). One hour later, both groups were divided into two sub-groups: CSExtinction and NoCSExtinction, with the former kept in CxB (FR1: 5-s CS, session duration up to extinction of responding on nicotine-paired lever, or max 6h), whereas the latter group was left in the home cage. After 24 hours, renewal test was performed in the original context (FR1: 5-s CS). A temporal analysis (15-min time bin) of responding during renewal revealed a statistically significant difference between Retrieval/CSExtinction vs. Retrieval/NoCSExtinction groups (P<0.05) at the first time bin, but no difference between NoRetrieval/CSExtinction and NoRetrieval/NoCSExtinction groups. These data suggest that if Pavlovian extinction is applied after retrieval may disrupt nicotine-memories reconsolidation.