Effects of repeated exposure to cocaine on group II metabotropic glutamate receptor function in the rat medial prefrontal cortex

Behavioral and neurochemical studies

Xiaohu Xie, Jeffery Steketee

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Rationale: Repeated exposure to cocaine progressively increases drug-induced locomotor activity, which is termed behavioral sensitization. Enhanced excitatory output from the medial prefrontal cortex (mPFC), which can be modulated by group II metabotropic glutamate receptors (mGluR), is thought to play a key role in the development of sensitization to cocaine. Objectives: The present studies were designed to determine whether the ability of intra-mPFC injections of the group II mGluR agonist 2R,4R-4-aminopyrrolidine-2,4- dicarboxylate (APDC) to inhibit cocaine-induced motor activity and dopamine release in the nucleus accumbens is reduced in sensitized animals. Results: Initial studies demonstrated that injection of APDC (0.015-15 nmol/side) into the mPFC dose dependently reduced cocaine-induced (15 mg/kg, i.p.) motor activity. The lowest dose in the present studies that significantly reduced the acute motor-stimulant response to cocaine was 1.5 nmol/side. The specificity of the effects of APDC was confirmed by demonstrating that intra-mPFC co-injection of LY341495 (1.5 nmol/side), a group II mGluR antagonist, prevented the inhibitory actions of APDC. Finally, it was shown that intra-mPFC injection of APDC was able to prevent the initiation of behavioral and neurochemical sensitization to cocaine. Intra-mPFC APDC was also observed to block the expression of cocaine-induced sensitization after short (1 day), but not prolonged (7 and 30 days), abstinence from cocaine. Conclusions: Taken together, these data suggest that mPFC group II mGluR function is reduced following extended abstinence from repeated cocaine.

Original languageEnglish (US)
Pages (from-to)501-510
Number of pages10
JournalPsychopharmacology
Volume203
Issue number3
DOIs
StatePublished - Apr 1 2009

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Metabotropic Glutamate Receptors
Prefrontal Cortex
Cocaine
Injections
LY 341495
Motor Activity
Excitatory Amino Acid Agonists
Excitatory Amino Acid Antagonists
Aptitude
Nucleus Accumbens
Locomotion
Dopamine

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

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abstract = "Rationale: Repeated exposure to cocaine progressively increases drug-induced locomotor activity, which is termed behavioral sensitization. Enhanced excitatory output from the medial prefrontal cortex (mPFC), which can be modulated by group II metabotropic glutamate receptors (mGluR), is thought to play a key role in the development of sensitization to cocaine. Objectives: The present studies were designed to determine whether the ability of intra-mPFC injections of the group II mGluR agonist 2R,4R-4-aminopyrrolidine-2,4- dicarboxylate (APDC) to inhibit cocaine-induced motor activity and dopamine release in the nucleus accumbens is reduced in sensitized animals. Results: Initial studies demonstrated that injection of APDC (0.015-15 nmol/side) into the mPFC dose dependently reduced cocaine-induced (15 mg/kg, i.p.) motor activity. The lowest dose in the present studies that significantly reduced the acute motor-stimulant response to cocaine was 1.5 nmol/side. The specificity of the effects of APDC was confirmed by demonstrating that intra-mPFC co-injection of LY341495 (1.5 nmol/side), a group II mGluR antagonist, prevented the inhibitory actions of APDC. Finally, it was shown that intra-mPFC injection of APDC was able to prevent the initiation of behavioral and neurochemical sensitization to cocaine. Intra-mPFC APDC was also observed to block the expression of cocaine-induced sensitization after short (1 day), but not prolonged (7 and 30 days), abstinence from cocaine. Conclusions: Taken together, these data suggest that mPFC group II mGluR function is reduced following extended abstinence from repeated cocaine.",
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AU - Steketee, Jeffery

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