Metabotropic glutamate 5 receptor blockade may attenuate cocaine self-administration by decreasing brain reward function in rats

Details

Serval ID
serval:BIB_1626BD4FF2E3
Type
Article: article from journal or magazin.
Collection
Publications
Title
Metabotropic glutamate 5 receptor blockade may attenuate cocaine self-administration by decreasing brain reward function in rats
Journal
Psychopharmacology
Author(s)
Kenny Paul J., Boutrel Benjamin, Gasparini Fabrizio, Koob George F., Markou Athina
ISSN
0033-3158
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
179
Number
1
Pages
247-254
Notes
SAPHIRID:67384
Abstract
RATIONALE: Evidence is accumulating that metabotropic glutamate 5 (mGlu5) receptors play an important role in regulating the reinforcing actions of drugs of abuse. OBJECTIVES: We examined the effects of the mGlu5 receptor antagonist MPEP on cocaine consumption and cocaine-enhanced brain reward function in rats. METHODS: Cocaine consumption was measured in rats with 1 h (short-access; ShA) or 6 h (long-access; LgA) daily access to intravenous cocaine (0.25 mg/infusion) self-administration. Cocaine-enhanced brain reward function was measured by cocaine-induced lowering of intracranial self-stimulation (ICSS) thresholds. RESULTS: Cocaine consumption remained stable and unaltered over successive self-administration sessions in ShA rats. In contrast, cocaine consumption progressively "escalated" in LgA rats. MPEP (1--9 mg/kg) dose-dependently decreased responding similarly in ShA and LgA rats. These data suggest that mGlu5 receptors regulate the reinforcing properties of cocaine, and that this action of mGlu5 receptors is independent of the escalation in consumption associated with extended access to cocaine self-administration. MPEP doses (1--9 mg/kg) that decreased cocaine self-administration elevated brain reward thresholds to a similar degree in cocaine- and vehicle-treated rats, indicating that MPEP induced a negative affective state. The additive effects of MPEP and cocaine on thresholds resulted in attenuation of the magnitude of cocaine-induced (10 mg/kg) lowering of ICSS thresholds. CONCLUSIONS: Overall, mGlu5 receptors appear to play an important role in regulating cocaine consumption, and also in regulating brain reward function. Further, it is likely that blockade of mGlu5 receptors may attenuate cocaine consumption, at least in part, by decreasing the baseline activity of brain reward circuitries.
Pubmed
Web of science
Create date
11/03/2008 15:07
Last modification date
20/08/2019 13:45
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