The influence of ionotropic and metabotropic glutamate receptor ligands on anxiety-like effect of amphetamine withdrawal in rats.

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.

• Authors: D Koltunowska, E Gibula-Bruzda, J H Kotlinska
• Journal: Progress in neuro-psychopharmacology & biological psychiatry (Prog Neuropsychopharmacol Biol Psychiatry) Vol. 45 Pg. 242-9 (Aug 01 2013) ISSN: 1878-4216 [Electronic] England
• PMID: 23623810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine
• Bridged Bicyclo Compounds
• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• Ligands
• Pyridines
• Receptors, Ionotropic Glutamate
• Receptors, Metabotropic Glutamate
• Thiazoles
• Taurine
• Amphetamine
• Acamprosate
• eglumetad
• Memantine

Topics

• Acamprosate
• Amphetamine (adverse effects)
• Animals
• Anxiety (complications, drug therapy)
• Bridged Bicyclo Compounds (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Excitatory Amino Acid Agonists (pharmacology, therapeutic use)
• Excitatory Amino Acid Antagonists (pharmacology, therapeutic use)
• Ligands
• Male
• Memantine (pharmacology, therapeutic use)
• Pyridines (pharmacology, therapeutic use)
• Rats
• Receptors, Ionotropic Glutamate (antagonists & inhibitors)
• Receptors, Metabotropic Glutamate (agonists, antagonists & inhibitors)
• Substance Withdrawal Syndrome (complications, drug therapy)
• Taurine (analogs & derivatives, pharmacology, therapeutic use)
• Thiazoles (pharmacology, therapeutic use)