Role Of IKK/NF-κB Signaling In Extinction Of Conditioned Place Aversion Memory

Objectives:To investigate the role of inhibitory kappa B kinase/transcription factor nuclear factor-kappa B (IKK/NF-κB) signaling in the drug associated aversive memory extinction, and making an advanced knowledge to the physiological role of IKK/NF-κB signaling in the different memory type. Those findings will provide help to understand the mechanism of pathological memory so that we can effectively prevent and cure the relapse of drug addiction.Methods:Study used morphine/naloxone conditioned place aversive (CPA) model. After CPA training, all rats received extinction training of CPA. Entail sulfasalazine (SSZ) to interfere progress of CPA extinction20min before training aiming to investigate the role of IKK/NF-κB signaling. The effects of sodium butyrate (NaB) on the inhibition of SSZ to the CPA extinction that will make an advanced knowledge to the mechanism underlying the IKK/NF-κB signaling activity. Some comparison experiments also are essential, for example, the effects of SSZ on locomotor activity of rats, the effects of SSZ on the acquisition and expression of CPA, the aversive or rewarding effects of SSZ, which will help us to exclude the confounding factors.Results:1. Inhibition of IKK/NF-κB pathway by SSZ suppressed the extinction of morphine withdrawal-associated aversive memory.2. The SSZ had no effects on the acquisition or expression of morphine withdrawal-associated aversive memory.3. NaB blocked the effect of SSZ on extinction of morphine-withdrawal associated aversive memory.4. The SSZ had no effects on the locomotor activity, and showed no aversive of rewarding effect per se. Conclusion:IKK/NF-κB signaling pathway might play a critical role in extinction of morphine withdrawal-associated memory and might be a potential pharmacotherapy target for opiate addiction.