Role of IKK/NF-κB signaling in extinction of conditioned place aversion memory in rats.
Bottom Line: 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.The blockade of CPA extinction induced by SSZ was abolished by sodium butyrate, an inhibitor of histone deacetylase.
Affiliation: Tianjin Medical University, Tianjin, China.
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.
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Mentions: To determine that the effect of SSZ on the extinction of morphine-induced CPA was not attributable to the possible side effects of SSZ (e.g., psychoactive actions), we investigated the effect of SSZ on locomotor activity and place preference in rats. Two groups of rats (n = 7−8 per group) were tested for changes in locomotor activity 20 min and 24 h after intracranial administration of SSZ (Fig. 4A). A repeated-measures ANOVA was used to analyze locomotor activity, with SSZ dose (0 and 10 mM) as the between-subjects factor and Test Condition (pretreatment, post-treatment, and re-test) as the within-subjects factor. The analysis revealed no significant effects of SSZ (F1,13 = 0.066, p>0.1) and no SSZ × Test Condition interaction (F2,26 = 1.383, p>0.1). These results suggest that the inhibition of IKK/NF-κB activity did not affect locomotor activity in rats (Fig. 4B).