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Role of the endogenous cannabinoid system as a modulator of dopamine transmission: Implications for Parkinson’s disease and schizophrenia

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Neurotoxicity Research : Volume 2

Neurotoxicity Research : Volume 1

Role of the endogenous cannabinoid system as a modulator of dopamine transmission: Implications for Parkinson’s disease and schizophrenia

Content Provider	Springer Nature Link
Author	Fonseca, Fernando Rodríguez de Gorriti, Miguel A. Bilbao, Ainhoa Escuredo, Leticia García segura, Luis Miguel Piomelli, Daniele Navarro, Miguel
Copyright Year	2001
Abstract	The endogenous cannabinoid system is a new signaling system composed by the central (CB$_{1}$) and the peripheral (CB$_{2}$) receptors, and several lipid transmitters including anandamide and 2-arachidonylg-lycerol. This system is the target of natural cannabinoids, the psychoactive constituents ofCannabis sativa preparations (marijuana, hashish). Acute and chronic cannabis exposure has been associated with subjective feelings of pleasure and relaxation, but also to the onset of psychiatric syndromes, a decrease of the efficacy of neuroleptics and alterations in the extrapyramidal system regulation of motor activity. These actions points to a tight association of the cannabinoid system with the brain dopaminergic circuits involved in addiction, the clinical manifestation of positive symptoms of schizophrenia and Parkinson’s disease. The present work discuss anatomical, biochemical and pharmacological evidences supporting a role for the endogenous cannabinoid system in the modulation of dopaminergic transmission. Cannabinoid CB$_{1}$ receptors are present in dopamine projecting brain areas. In primates and certain rat strains it is also located in dopamine cells of the A8, A9 and A10 mesencephalic cell groups, as well as in hypothalamic dopaminergic neurons controlling prolactin secretion. CB$_{1}$ receptors co-localize with dopamine D$_{1}$/D$_{2}$ receptors in dopamine projecting fields. Manipulation of dopaminergic transmission is able of altere the synthesis and release of anandamide as well as the expression of CB$_{1}$ receptors. Additionally, CB$_{1}$receptors can switch its transduction mechanism to oppose to the ongoing dopamine signaling. Acute blockade of CB$_{1}$ receptor potentiates the facilitatory role of dopamine D$_{2}$ receptor agonists on movement. CB$_{1}$ stimulation results in sensitization to the motor effects of indirect dopaminergic agonists. The dynamics of these changes indicate that the cannabinoid system is an activity-dependent modulator of dopaminergic transmission, an hypothesis relevant for the design of new therapeutic strategies for dopamine-related diseases such as the psychosis and Parkinson’s disease.
Starting Page	23
Ending Page	35
Page Count	13
File Format	PDF
ISSN	10298428
Journal	Neurotoxicity Research
Volume Number	3
Issue Number	1
e-ISSN	14763524
Language	English
Publisher	Springer-Verlag
Publisher Date	2001-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Neurosciences Pharmaceutical Sciences/Technology Neurology Neurochemistry Pharmacology/Toxicology Neurobiology
Content Type	Text
Resource Type	Article
Subject	Neuroscience Toxicology

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