Extinction training during reconsolidation window: Key to attenuation of cocaine memories Smith AL, Sartor GC, and Aston-Jones G

Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA

Introduction

Support contributed by R01DA017289 and T32 DA007288.

Methods

Results

Future Studies

Acknowledgements

Summary

Extinction training during reconsolidation window blocks cocaine-primed reinstatement of cocaine preference

Figure 1. Starting extinction training 1 hour after cocaine contextual memory was retrieved (during the reconsolidation window) significantly blocked cocaine-primed reinstatement of a cocaine preference (*p<0.01). No significant difference in expression of cocaine preference or extinction was observed between the two groups.

Number of extinction sessions prior to reinstatement test

Figure 2. No difference in the number of extinction sessions was observed between retrieval (Ret) and no retrieval (No Ret) groups. Rats received passive extinction training by re-testing (drug-free) for cocaine preference (one session a day) until there was no cocaine preference for 3 consecutive sessions.

Memories are initially labile when formed but become consolidated via synthesis of new proteins. Retrieval of a consolidated memory can activate two opposing mechanisms: reconsolidation or extinction. During reconsolidation, the retrieved memory returns to a labile state in which the memory is susceptible to enhancement or disruption. The period of lability (reconsolidation window) may last for several hours. In contrast, extinction is a form of new learning that inhibits a memory.

Recent results from LeDoux and colleagues revealed that starting extinction training during the reconsolidation window (1hr after the memory has been retrieved) significantly attenuates fear memories in rats and humans (Monfils et al. 2009, Science; Schiller et al. 2010, Nature) .

Here we use a similar non-invasive design to try to attenuate contextual cocaine memories by taking advantage of the differences between reconsolidation and extinction

Conditioned place preference (CPP): On the first day (pre-test), male Sprague Dawley rats (300-325g) rats had free access to both sides of the chamber for 15 min (drug-free). The time spent on each side of the chamber was recorded automatically. Two days later, conditioning occurred over 3 consecutive days. During conditioning, rats received daily injections (i.p.) of cocaine (10 mg/kg) and saline (one in AM, one in PM) and were confined to corresponding sides of the chamber for 30 min. Retrieval: Two days after the last conditioning day, the cocaine memory was retrieved or not by a 3 minute exposure to the cocaine-paired side (Ret) or the saline-paired side (No Ret), respectively. One hour after memory retrieval (during the reconsolidation window), rats were tested for cocaine-place preference by allowing free access to both sides of the chamber for 15 min. Because there is no drug available during the test, the expression test is also considered the first extinction test. Extinction: Rats received passive extinction training by re-testing (drug-free) for cocaine preference (one session a day) until there was no cocaine preference for 3 consecutive sessions. Reinstatement: One day after extinction criteria was met, rats received a cocaine injection (10mg/kg i.p.) to reinstate the cocaine preference.

Ø  Beginning extinction training during the reconsolidation window significantly blocked cocaine-primed reinstatement of a cocaine preference. Ø  No difference in expression of cocaine preference was observed between Ret and No Ret animals. Ø  No difference in rate of extinction was observed between Ret and No Ret animals.

Ø  Determine if this paradigm will disrupt memory savings of a cocaine place preference.

Ø  Determine if this paradigm will attenuate contextual induced reinstatement of cocaine self-administration.

Ø  Determine the molecular mechanisms and/or brain regions involved in this paradigm.

1 2 3 4 5-100

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Expression Test

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