| Literature DB >> 23623810 |
D Koltunowska1, E Gibula-Bruzda, J H Kotlinska.
Abstract
Chronic amphetamine use results in anxiety-like states after drug cessation. The aim of the study was to determine a role of ionotropic and metabotropic glutamate receptor ligands in amphetamine-evoked withdrawal anxiety in the elevated plus-maze test in rats. In our study memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist did not reduce amphetamine withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate 5 receptor (mGluR5) antagonist) at the dose 200 and 400mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and a number of open arm entries. mGluR5 selective antagonist, MTEP (3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine hydrochloride) and mGluR2/3 agonist, LY354740 (1S,2S,5R,6S)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid), caused effects similar to acamprosate at doses 1.25-5mg/kg and 2.5-5mg/kg, respectively. None of the glutamate ligands influenced locomotor activity of rats when given to the saline-treated group. Taking into account the positive correlation between amphetamine withdrawal-induced anxiety and relapse to amphetamine taking, our results suggest that modulation of mGluRs may prevent relapse to amphetamine and might pose a new direction in amphetamine abuse therapy.Entities:
Keywords: AMPA; ANOVA; Acamprosate; Amphetamine withdrawal; Anxiolytic-like activity; GABA; LY354740; MTEP; Memantine; N-methyl-d-aspartate; NMDA; SEM; analysis of variance; iGluRs; intraperitoneal injection; ionotropic glutamate receptors; ip; mGluRs; metabotropic glutamate receptors; standard error of the mean; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; γ-aminobutyric acid
Mesh：
Substances：
Year: 2013 PMID： 23623810 DOI： 10.1016/j.pnpbp.2013.04.013
Source DB: PubMed Journal: Prog Neuropsychopharmacol Biol Psychiatry ISSN： 0278-5846 Impact factor: 5.067