title: 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.affiliation: Department of Pharmacology and Pharmacodynamics, Medical University, Lublin, Poland. d.koltunowska@umlub.pl
authors.forename: D
authors.initials: D
authors.lastname: Koltunowska
authors.forename: E
authors.initials: E
authors.lastname: Gibula-Bruzda
authors.forename: J H
authors.initials: JH
authors.lastname: Kotlinska
mesh_terms: D000077443:Acamprosate; D000661:Amphetamine / Q000009:adverse effects*; D000818:Animals; D001007:Anxiety / Q000150:complications / Q000188:drug therapy*; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D008024:Ligands; D008297:Male; D008559:Memantine / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D058468:Receptors, Ionotropic Glutamate / Q000037:antagonists & inhibitors*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000188:drug therapy*; D013654:Taurine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D013844:Thiazoles / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C472365:3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine; D001643:Bridged Bicyclo Compounds; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D011725:Pyridines; D058468:Receptors, Ionotropic Glutamate; D018094:Receptors, Metabotropic Glutamate; D013844:Thiazoles; D013654:Taurine; D000661:Amphetamine; D000077443:Acamprosate; C104753:eglumetad; D008559:Memantine
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