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Methamphetamine-induced changes in the striatal dopamine pathway in μ-opioid receptor knockout mice

DOI: 10.1186/1423-0127-18-83

Keywords: Amphetamine, μ-opioid receptor, addiction, dopamine receptors

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Abstract:

The present study determined whether resistance of the μ-opioid receptor (μ-OR) knockout mice to behavioral sensitization is due to differential expression of the stimulatory G protein α subunit (Gαs) or regulators of G-protein signaling (RGS) coupled to the dopamine D1 receptor. Mice received daily intraperitoneal injections of saline or METH (10 mg/kg) for 7 consecutive days to induce sensitization. On day 11(following 4 abstinent days), mice were either given a test dose of METH (10 mg/kg) for behavioral testing or sacrificed for neurochemical assays without additional METH treatment.METH challenge-induced stereotyped behaviors were significantly reduced in the μ-opioid receptor knockout mice when compared with those in wild-type mice. Neurochemical assays indicated that there is a decrease in dopamine D1 receptor ligand binding and an increase in the expression of RGS4 mRNA in the striatum of METH-treated μ-opioid receptor knockout mice but not of METH-treated wild-type mice. METH treatment had no effect on the expression of Gαs and RGS2 mRNA in the striatum of either strain of mice.These results indicate that down-regulation of the expression of the dopamine D1 receptor and up-regulation of RGS4 mRNA expression in the striatum may contribute to the reduced response to METH-induced stereotypy behavior in μ-opioid receptor knockout mice. Our results highlight the interactions of the μ-opioid receptor system to METH-induced behavioral responses by influencing the expression of RGS of dopamine D1 receptors.Methamphetamine (METH) is a highly abused CNS stimulant with high reward properties that leads to compulsive drug seeking behavior [1,2]. The mechanism of the additive properties to METH remains to be determined. Repeated administration of METH results in behavioral sensitization characterized by persistent hyperlocomotor activity and stereotyped behaviors [3,4]. Animals remain sensitized for many weeks, suggesting that the development of sensitization involves l

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