Dissociable roles of mGlu5 and dopamine receptors in the rewarding and sensitizing properties of morphine and cocaine

Rationale Drugs of abuse are initially used because of their rewarding properties. As a result of repeated drug exposure, sensitization to certain behavioral effects of drugs occurs, which may facilitate the development of addiction. Recent studies have implicated the metabotropic glutamate receptor...

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Bibliographic Details
Published in:Psychopharmacologia 2011-04, Vol.214 (4), p.863-876
Main Authors: Veeneman, M. M. J., Boleij, H., Broekhoven, M. H., Snoeren, E. M. S., Guitart Masip, M., Cousijn, J., Spooren, W., Vanderschuren, L. J. M. J.
Format: Article
Language:English
Subjects:
Analysis
Animals
Behavior, Animal - drug effects
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cocaine
Cocaine - pharmacology
Dopamine Antagonists - pharmacology
Dopamine receptors
Dose-Response Relationship, Drug
Flupenthixol - pharmacology
Glutamate
Illegal drugs
Male
Medical sciences
Morphine
Morphine - pharmacology
Motor Activity - drug effects
Neuropharmacology
Neurosciences
Neurotransmitters
Original Investigation
Pharmacology. Drug treatments
Pharmacology/Toxicology
Phenols
Psychiatry
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
Psychotropic drugs
Pyridines - pharmacology
Rats
Rats, Wistar
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate - antagonists & inhibitors
Receptors, Metabotropic Glutamate - physiology
Reward
Thiazoles - pharmacology
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Summary:Rationale Drugs of abuse are initially used because of their rewarding properties. As a result of repeated drug exposure, sensitization to certain behavioral effects of drugs occurs, which may facilitate the development of addiction. Recent studies have implicated the metabotropic glutamate receptor 5 (mGlu5 receptor) in drug reward, but its role in sensitization is unclear. Stimulation of dopamine receptors plays an important role in drug reward, but not in the sensitizing properties of cocaine and morphine. Objective This study aims to evaluate the role of mGlu5 and dopamine receptors in the development of cocaine- and morphine-induced conditioned place preference (CPP) and psychomotor sensitization. Materials and methods Rats were treated with the mGlu5 receptor antagonist MTEP (0, 1, 3, and 10 mg/kg, i.p.) or the dopamine receptor antagonist α-flupenthixol (0, 0.125, 0.25, and 0.5 mg/kg, i.p.) during place conditioning with either morphine (3 mg/kg, s.c.) or cocaine (15 mg/kg, i.p.). Furthermore, MTEP (1 mg/kg, i.p.) or α-flupenthixol (0.5 mg/kg, i.p.) was co-administered during cocaine (30 mg/kg, i.p.) or morphine (3.0 mg/kg, s.c.) pretreatment and psychomotor sensitization was tested 3 weeks post-treatment. Results MTEP attenuated the development of morphine- but not cocaine-induced CPP. In contrast, MTEP suppressed the development of cocaine- but not morphine-induced psychomotor sensitization. α-Flupenthixol blocked the development of both cocaine- and morphine-induced CPP but did not affect the development of sensitization to either drug. Conclusion Dopamine receptor stimulation mediates cocaine and morphine reward but not sensitization. In contrast, the role of mGlu5 receptors in reward and sensitization is drug-specific.
ISSN:0033-3158
1432-2072
DOI:10.1007/s00213-010-2095-1