Abstract
The contribution of the endocannabinoid system to dopamine-mediated disorganized behavior in schizophrenia is discussed. We used a model of concurrent stimulation of dopamine D1 and D2 receptors to evaluate the role of this system in dopamine-mediated stereotypies measured in a hole-board test. Pretreatment with the cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichloro-phenyl)-4-methyl-1H-pyrazole-3-carboxamide (SR141716A; 1 mg/kg) potentiated stereotyped behavior induced by coadministration of the dopamine D1 receptor agonist SKF 38393 (0.05, 0.1 and 1 mg/kg) and the dopamine D2 receptor agonist quinpirole (0.25 mg/kg). Thus, the endocannabinoid system acts as a brake for abnormal behavior associated with dopaminergic overactivation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / pharmacology
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Animals
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Behavior, Animal / drug effects*
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Dopamine Agonists / pharmacology*
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Dose-Response Relationship, Drug
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Male
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Piperidines / pharmacology*
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Pyrazoles / pharmacology*
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Quinpirole / pharmacology
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Rats
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Rats, Wistar
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Receptor, Cannabinoid, CB1 / antagonists & inhibitors*
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Receptor, Cannabinoid, CB1 / metabolism
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Receptors, Dopamine / drug effects*
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Receptors, Dopamine / metabolism
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Receptors, Dopamine D1 / agonists
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Receptors, Dopamine D2 / agonists
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Rimonabant
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Schizophrenia / metabolism
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Schizophrenic Psychology
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Stereotyped Behavior / drug effects*
Substances
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Dopamine Agonists
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Piperidines
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Pyrazoles
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Receptor, Cannabinoid, CB1
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Receptors, Dopamine
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Quinpirole
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2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine
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Rimonabant