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THE GROUP II METABOTROPIC GLUTAMATE AGONIST, LY379268, DECREASES METHAMPHETAMINE SELF-ADMINISTRATION IN RATS

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abstract
Rationale: Methamphetamine (METH) abuse is a growing problem worldwide, for which there is no effective pharmacotherapy. Group II metabotropic glutamate receptor (mGluR) agonists are proposed to serve as an addiction treatment and have been shown to reduce the reinforcing properties of cocaine, but their efficacy has yet to be tested in METH. Objectives: The present study investigated the efficacy of a selective group II mGluR agonist (LY379268) in reducing METH self-administration in a well-established animal model of drug abuse. Methods: The effects of LY379268 on progressive ratio breakpoints for METH or food were assessed. Rats were trained to self-administer either METH or a control reinforcer (food) on a progressive ratio schedule. Rats were pretreated with vehicle (Veh) or LY379268 (0.01, 0.1, 0.3, 1.0 mg/kg, i.p.) 30 minutes before the behavioral session. Additionally, METH trained rats underwent two weeks of 6 hour METH access, after which the efficacy of LY379268 in reducing METH self-administration was assessed. Results: Rats increased their daily METH intake over the course of 14 days of exposure to 6 hour sessions. Systemic pretreatment with LY379268 dose-dependently inhibited METH self-administration in animals with limited and extended METH histories but had no effect on food self-administration at the doses tested. There was no significant difference in sensitivity to the effects of LY379268 before and after escalation. Conclusions: These results indicate a role for group II mGluR in mediating the reinforcing effects of METH. Furthermore, they support the notion that group II mGluR agonists may be potential pharmacotherapies for METH dependence.
subject
Glutamate
LY379268
Methamphetamine
Rat
Self-Administration
contributor
Crawford, Jordan Thomas (author)
Roberts, David C.S. (committee chair)
Jones, Sara R. (committee member)
date
2012-01-18T09:35:34Z (accessioned)
2012-07-18T08:30:15Z (available)
2011 (issued)
degree
Neuroscience (discipline)
embargo
2012-07-18 (terms)
identifier
http://hdl.handle.net/10339/36442 (uri)
language
en (iso)
publisher
Wake Forest University
title
THE GROUP II METABOTROPIC GLUTAMATE AGONIST, LY379268, DECREASES METHAMPHETAMINE SELF-ADMINISTRATION IN RATS
type
Thesis

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