Arvanil, a hybrid endocannabinoid and vanilloid compound, behaves as an antihyperkinetic agent in a rat model of Huntington's disease.
The present study was designed to examine whether arvanil (N-arachidonoyl-vanillyl-amide), an endocannabinoid/vanilloid structural "hybrid", might provide symptom relief in the rat model of Huntington's disease (HD) generated by bilateral intrastriatal application of 3-nitropropionic acid (3-NP), where previous evidence suggests that hybrid cannabinoid/vanilloid compounds might be effective. As expected, arvanil did reduce ambulation, stereotypic activity, and number of hole entries, and increased the inactivity, in control rats. It was also active in 3-NP-lesioned rats, where, despite its lowering effects on stereotypic activity and number of hole entries, arvanil reduced the hyperkinesia (increased ambulation) typical of these rats, and also increased the inactivity, these two effects being more moderate than those found in control rats. Arvanil caused its antihyperkinetic effects in 3-NP-lesioned rats presumably by enhancing excitatory transmission at the globus pallidus, since it increased glutamate content in this region. This contrasts with its effects in control rats where arvanil enhanced GABA transmission at the globus pallidus. In summary, arvanil does alleviate hyperkinesia typical of HD, although it also affects locomotion in normal rats. Nevertheless, considering the lack of efficacious pharmacological treatments in this basal ganglia disorder, our findings might provide the basis for the development of more specific drugs against HD.
de Lago
Eva
E
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Complutense, 28040-Madrid, Spain.
Urbani
Paolo
P
Ramos
José Antonio
JA
Di Marzo
Vincenzo
V
Fernández-Ruiz
Javier
J
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives* / Q000494:pharmacology; D003292:Convulsants; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006816:Huntington Disease / Q000139:chemically induced / Q000188:drug therapy*; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009574:Nitro Compounds; D011422:Propionates; D051381:Rats; D017207:Rats, Sprague-Dawley; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D003292:Convulsants; D009574:Nitro Compounds; D011422:Propionates; C121153:arvanil; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C015392:3-nitropropionic acid; D002211:Capsaicin; D004298:Dopamine