Abstract
The inhibitor κB protein kinase/nuclear factor κB (IKK/NF-κB) signaling pathway is critical for synaptic plasticity. However, the role of IKK/NF-κB in drug withdrawal-associated conditioned place aversion (CPA) memory is unknown. Here, we showed that inhibition of IKK/NF-κB by sulphasalazine (SSZ; 10 mM, i.c.v.) selectively blocked the extinction but not acquisition or expression of morphine-induced CPA in rats. The blockade of CPA extinction induced by SSZ was abolished by sodium butyrate, an inhibitor of histone deacetylase. Thus, the IKK/NF-κB signaling pathway might play a critical role in the extinction of morphine-induced CPA in rats and might be a potential pharmacotherapy target for opiate addiction.
Highlights
Opiate addiction is a chronic relapsing disorder characterized by compulsive drug seeking and taking motivated by the desire to experience the hedonic effects of the drug and to avoid the aversive consequences of drug withdrawal [1,2,3]
The results revealed significant effects of SSZ dose (F2,29 = 4.090, p,0.05) and test condition (F2,58 = 91.97, p,0.001) and a treatment 6 test condition interaction (F4,58 = 4.399, p,0.01; Fig. 1B). These results indicate that SSZ-induced (10 mM, i.c.v.) inhibition of IkB kinase (IKK)/nuclear factor kB (NF-kB) suppressed the extinction of morphine withdrawalassociated aversive memory
We found that blockade of the IKK/NF-kB signaling pathway by intracerebroventricular SSZ infusion selectively suppressed the extinction but not acquisition or expression of morphine withdrawal-associated conditioned place aversion (CPA), which was blocked by pretreatment with an histone deacetylase (HDAC) inhibitor, sodium butyrate
Summary
Opiate addiction is a chronic relapsing disorder characterized by compulsive drug seeking and taking motivated by the desire to experience the hedonic effects of the drug and to avoid the aversive consequences of drug withdrawal [1,2,3]. Drug withdrawal-induced aversive memories have been proposed to play an important role in the compulsivity associated with drug seeking and taking [4,5,6]. Morphine withdrawal-induced conditioned place aversion (CPA) memory has been widely used in animals to investigate the negative consequences by drug withdrawal [7,8]. Behavioral extinction training effectively abolished the expression of morphine-induced CPA [7]. The exploration of the underlying mechanism is important to prevent relapse induced by anhedonia and the aversive consequences of drug withdrawal
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