Behavioural and biochemical responses to methamphetamine are differentially regulated by mGlu2 and mGlu3 metabotropic glutamate receptors in male mice.

Autor: Busceti CL; IRCCS Neuromed, Pozzilli, Italy., Ginerete RP; IRCCS Neuromed, Pozzilli, Italy., Di Menna L; IRCCS Neuromed, Pozzilli, Italy., D'Errico G; IRCCS Neuromed, Pozzilli, Italy., Cisani F; Department of Pharmacy, University of Genova, Genova, Italy., Di Pietro P; IRCCS Neuromed, Pozzilli, Italy., Imbriglio T; IRCCS Neuromed, Pozzilli, Italy., Bruno V; IRCCS Neuromed, Pozzilli, Italy; Department of Physiology and Pharmacology, University Sapienza, Roma, Italy., Battaglia G; IRCCS Neuromed, Pozzilli, Italy; Department of Physiology and Pharmacology, University Sapienza, Roma, Italy., Fornai F; IRCCS Neuromed, Pozzilli, Italy; Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy., Monn JA; IRCCS Neuromed, Pozzilli, Italy., Pittaluga A; Department of Pharmacy, University of Genova, Genova, Italy; IRCCS Ospedale Policlinico San Martino, Genova, Italy., Nicoletti F; IRCCS Neuromed, Pozzilli, Italy; Department of Physiology and Pharmacology, University Sapienza, Roma, Italy. Electronic address: nicoletti@neuromed.it.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2021 Sep 15; Vol. 196, pp. 108692. Date of Electronic Publication: 2021 Jul 01.
DOI: 10.1016/j.neuropharm.2021.108692
Abstrakt: Group II metabotropic glutamate receptors (mGlu2 and mGlu3 receptors) shape mechanisms of methamphetamine addiction, but the individual role played by the two subtypes is unclear. We measured methamphetamine-induced conditioned place preference (CPP) and motor responses to single or repeated injections of methamphetamine in wild-type, mGlu2 -/- , and mGlu3 -/- mice. Only mGlu3 -/- mice showed methamphetamine preference in the CPP test. Motor response to the first methamphetamine injection was dramatically reduced in mGlu2 -/- mice, unless these mice were treated with the mGlu5 receptor antagonist, MTEP. In contrast, methamphetamine-induced sensitization was increased in mGlu3 -/- mice compared to wild-type mice. Only mGlu3 -/- mice sensitized to methamphetamine showed increases in phospho-ERK1/2 levels in the nucleus accumbens (NAc) and free radical formation in the NAc and medial prefrontal cortex. These changes were not detected in mGlu2 -/- mice. We also measured a series of biochemical parameters related to the mechanism of action of methamphetamine in naïve mice to disclose the nature of the differential behavioural responses of the three genotypes. We found a reduced expression and activity of dopamine transporter (DAT) and vesicular monoamine transporter-2 in the NAc and striatum of mGlu2 -/- and mGlu3 -/- mice, whereas expression of the DAT adaptor, syntaxin 1A, was selectively increased in the striatum of mGlu3 -/- mice. Methamphetamine-stimulated dopamine release in striatal slices was largely reduced in mGlu2 -/- , but not in mGlu3 -/- , mice. These findings suggest that drugs that selectively enhance mGlu3 receptor activity or negatively modulate mGlu2 receptors might be beneficial in the treatment of methamphetamine addiction and associated brain damage.
(Copyright © 2021. Published by Elsevier Ltd.)
Databáze: MEDLINE
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