Thioredoxin-1 downregulation in nucleus accumbens promotes methamphetamine-primed reinstatement in mice.

Thioredoxin-1 downregulation in nucleus accumbens promotes methamphetamine-primed reinstatement in mice. Neuropharmacology. 2018 Jul 04;: Authors: Huang M, Yan C, Yang X, Zhou X, Lv W, Guo N, Li Y, Bai J Abstract Relapse of drug abuse after abstinence is a major challenge to the treatment of addicts. Thioredoxin-1 (Trx-1) is an important regulator of neuroprotection, and inhibits morphine-induced hyperlocomotion, reward and withdrawal signs, as well as blocks methamphetamine (METH)-induced conditioned place preference (CPP). Nucleus accumbens (NAc) is essential for relapse like behavior in reinstatement animal models. In the present study, we aim to investigate the role of Trx-1 in NAc in METH-primed reinstatement by using a reinstatement procedure in mice. Adeno-associated virus vectors expressing shRNA-mTrx-1 (AAV-shRNA-mTrx-1) were bilaterally microinjected into the NAc after METH-CPP extinction. The results showed that Trx-1 downregulation in NAc promoted the reinstatement of METH-CPP. We also examined the expression of N-methyl-D-asparate (NMDA) receptor 2B subunit (GluN2b), the levels of phosphorylated extracellular signal-regulated kinase (p-ERK) and phosphorylated cAMP-response element binding protein (p-CREB) in the NAc by western blot analysis, and found that the GluN2b expression, p-ERK and p-CREB levels were increased in the NAc in response to low-dose METH in AAV-shRNA-mTrx-1 mice, but were not changed in control and AAV...
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research