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Role of IKK/NF-κB signaling in extinction of conditioned place aversion memory in rats.

Yang CH, Liu XM, Si JJ, Shi HS, Xue YX, Liu JF, Luo YX, Chen C, Li P, Yang JL, Wu P, Lu L - PLoS ONE (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Tianjin Medical University, Tianjin, China.

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.

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Related in: MedlinePlus

Sulfasalazine had no effect on locomotor activity and no aversive or rewarding effects.(A) Timeline of effects of SSZ on locomotor activity. Locomotor activity was tested 20 min (Post-T) and 24 h (Re-T) after SSZ administration (10 mM) for 5 min. (B) Sulfasalazine (10 mM) did not affect locomotor activity 20 min or 24 h after infusion. (C) Timeline of SSZ-induced conditioned place preference/aversive procedure. A double 2-day-session training procedure was used to test the aversive or rewarding effects of SSZ. (D) Sulfasalazine did not induce any aversion to or preference for the drug-paired chamber (CPA score), indicating that SSZ had no aversive or rewarding effects. The data are expressed as mean ± SEM. Pre-T, pre-treatment; Post-T, post-treatment; Re-T, re-test.
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pone-0039696-g004: Sulfasalazine had no effect on locomotor activity and no aversive or rewarding effects.(A) Timeline of effects of SSZ on locomotor activity. Locomotor activity was tested 20 min (Post-T) and 24 h (Re-T) after SSZ administration (10 mM) for 5 min. (B) Sulfasalazine (10 mM) did not affect locomotor activity 20 min or 24 h after infusion. (C) Timeline of SSZ-induced conditioned place preference/aversive procedure. A double 2-day-session training procedure was used to test the aversive or rewarding effects of SSZ. (D) Sulfasalazine did not induce any aversion to or preference for the drug-paired chamber (CPA score), indicating that SSZ had no aversive or rewarding effects. The data are expressed as mean ± SEM. Pre-T, pre-treatment; Post-T, post-treatment; Re-T, re-test.

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).


Role of IKK/NF-κB signaling in extinction of conditioned place aversion memory in rats.

Yang CH, Liu XM, Si JJ, Shi HS, Xue YX, Liu JF, Luo YX, Chen C, Li P, Yang JL, Wu P, Lu L - PLoS ONE (2012)

Sulfasalazine had no effect on locomotor activity and no aversive or rewarding effects.(A) Timeline of effects of SSZ on locomotor activity. Locomotor activity was tested 20 min (Post-T) and 24 h (Re-T) after SSZ administration (10 mM) for 5 min. (B) Sulfasalazine (10 mM) did not affect locomotor activity 20 min or 24 h after infusion. (C) Timeline of SSZ-induced conditioned place preference/aversive procedure. A double 2-day-session training procedure was used to test the aversive or rewarding effects of SSZ. (D) Sulfasalazine did not induce any aversion to or preference for the drug-paired chamber (CPA score), indicating that SSZ had no aversive or rewarding effects. The data are expressed as mean ± SEM. Pre-T, pre-treatment; Post-T, post-treatment; Re-T, re-test.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3383688&req=5

pone-0039696-g004: Sulfasalazine had no effect on locomotor activity and no aversive or rewarding effects.(A) Timeline of effects of SSZ on locomotor activity. Locomotor activity was tested 20 min (Post-T) and 24 h (Re-T) after SSZ administration (10 mM) for 5 min. (B) Sulfasalazine (10 mM) did not affect locomotor activity 20 min or 24 h after infusion. (C) Timeline of SSZ-induced conditioned place preference/aversive procedure. A double 2-day-session training procedure was used to test the aversive or rewarding effects of SSZ. (D) Sulfasalazine did not induce any aversion to or preference for the drug-paired chamber (CPA score), indicating that SSZ had no aversive or rewarding effects. The data are expressed as mean ± SEM. Pre-T, pre-treatment; Post-T, post-treatment; Re-T, re-test.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Tianjin Medical University, Tianjin, China.

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.

Show MeSH
Related in: MedlinePlus