Experimental parkinsonism alters anandamide precursor synthesis, and functional deficits are improved by AM404: a modulator of endocannabinoid function

Autor: Fadwa El Banoua, Beatriz Galan-Rodriguez, Juan A. Flores, Belen Ferrer, Isabel Caraballo, Fernando Rodríguez de Fonseca, Emilio Fernández-Espejo
Rok vydání: 2004
Předmět:
Male
medicine.medical_treatment
Cell Count
Functional Laterality
Antiparkinson Agents
chemistry.chemical_compound
Piperidines
Drug Interactions
Behavior
Animal
Dopaminergic
Anandamide
Endocannabinoid system
Serotonin Receptor Agonists
Substantia Nigra
Psychiatry and Mental health
Dopamine receptor
AM404
Dopamine Agonists
lipids (amino acids
peptides
and proteins)
Serotonin Antagonists
medicine.drug
medicine.medical_specialty
Rotation
Tyrosine 3-Monooxygenase
Polyunsaturated Alkamides
Arachidonic Acids
Motor Activity
Dopamine agonist
Drug Administration Schedule
Amidohydrolases
Parkinsonian Disorders
Dopamine
Internal medicine
medicine
Animals
Rats
Wistar
Oxidopamine
Pharmacology
Brain Chemistry
Analysis of Variance
Dose-Response Relationship
Drug
Rats
Amphetamine
Endocrinology
chemistry
Dopamine Antagonists
Pyrazoles
Central Nervous System Stimulants
Cannabinoid
Acyltransferases
Endocannabinoids
Zdroj: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. 29(6)
ISSN: 0893-133X
Popis: Modulation of the endocannabinoid system might be useful in treating Parkinson's disease. Here, we show that systemic administration of N-(4-hydroxyphenyl)-arachidonamide (AM404), a cannabinoid modulator that enhances anandamide (AEA) availability in the biophase, exerts antiparkinsonian effects in 6-hydroxydopamine-lesioned rats. Local injections of AM404 into denervated striata reduced parkinsonian motor asymmetries, these effects being associated with the reduction of D2 dopamine receptor function together with a positive modulation of 5-HT(1B) serotonin receptor function. Stimulation of striatal 5-HT(1B) receptors alone was observed to ameliorate parkinsonian deficits, supporting the fact that AM404 exerts antiparkinsonian effects likely through stimulation of striatal 5-HT(1B) serotonin receptor function. Hence, modulation of cannabinoid function leading to enhancement of AEA in the biophase might be of therapeutic value in the control of symptoms of Parkinson's disease. On the other hand, reduced levels of N-acyl-transferase (AEA precursor synthesizing enzyme), without changes in fatty acid amidohydrolase (AEA degradative enzyme), were detected in denervated striata in comparison with intact striata. This finding reveals the presence of a homeostatic striatal mechanism emerging after dopaminergic denervation likely tending to enhance low dopamine tone.
Databáze: OpenAIRE
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