Regulation of cocaine-induced reinstatement by group II metabotropic glutamate receptors in the ventral tegmental area

Lianyi Lu, Yueqiang Xue, Jeffery Steketee, George V. Rebec, Wen Lin Sun

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13 Citations (Scopus)

Abstract

Rationale A high rate of relapse is a daunting challenge facing clinical treatment of cocaine addiction. Recent studies have shown that drugs of abuse enhance glutamate neurotransmission in dopamine neurons in the ventral tegmental area (VTA) and such enhancement may contribute to the risk of relapse. Objectives Given the important role of group II metabo-tropic glutamate receptors (mGluR2/3s) in regulating glutamate release from the glutamatergic terminals, this study aimed to test whether activation of mGluR2/3s in the VTA can inhibit cocaine-induced reinstatement of cocaine-seeking behavior, a model of relapse to drug-seeking behavior. Methods Rats were trained to self-administer intravenous cocaine (0.25 mg/infusion) under a modified fixed-ratio 5 schedule. After rats reached the training criteria, they went through extinction training to extinguish cocaine-seeking behavior. Then the dose-response effects of a selective mGluR2/3 agonist LY 379268 microinjected into the VTA on cocaine-induced reinstatement of cocaine-seeking behavior were assessed. Results LY 379268 (0.032-0.1 μg/side) dose-dependently decreased cocaine-induced reinstatement. The effect could not be fully attributed to diffusion of the drug to the neighboring substantia nigra or to motor impairment. Interestingly, LY 379268 has a less potent effect on cocaine-induced reinstatement than on sucrose-induced reinstatement of sucrose-seeking behavior. Conclusions Our data support the idea that glutamate release in the VTA is critically involved in cocaine-induced reinstatement and indicate that loss of mGluR2/3-mediated regulation of glutamate release in the VTA may critically contribute to the risk of relapse.

Original languageEnglish (US)
Pages (from-to)75-85
Number of pages11
JournalPsychopharmacology
Volume220
Issue number1
DOIs
StatePublished - Mar 1 2012

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Ventral Tegmental Area
Metabotropic Glutamate Receptors
Cocaine
LY 379268
Glutamic Acid
Recurrence
Sucrose
Drug-Seeking Behavior
Cocaine-Related Disorders
Dopaminergic Neurons
Glutamate Receptors
Street Drugs
Substantia Nigra
Synaptic Transmission
Appointments and Schedules
metabotropic glutamate receptor 2

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Regulation of cocaine-induced reinstatement by group II metabotropic glutamate receptors in the ventral tegmental area. / Lu, Lianyi; Xue, Yueqiang; Steketee, Jeffery; Rebec, George V.; Sun, Wen Lin.

In: Psychopharmacology, Vol. 220, No. 1, 01.03.2012, p. 75-85.

Research output: Contribution to journalArticle

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