Cannabinoid CB1 receptor antagonism markedly increases dopamine receptor-mediated stereotypies.
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.
Ferrer
Belen
B
Fundación IMABIS, Hospital Carlos Haya, Málaga 29010, Spain.
Gorriti
Miguel Angel
MA
Palomino
Ana
A
Gornemann
Isolde
I
de Diego
Yolanda
Y
Bermudez-Silva
Francisco Javier
FJ
Bilbao
Ainhoa
A
Fernandez-Espejo
Emilio
E
Moratalla
Rosario
R
Navarro
Miguel
M
Rodríguez de Fonseca
Fernando
F
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists; D017448:Receptors, Dopamine D2 / Q000819:agonists; D000077285:Rimonabant; D012559:Schizophrenia / Q000378:metabolism; D012565:Schizophrenic Psychology; D013239:Stereotyped Behavior / Q000187:drug effects*
D018491:Dopamine Agonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D000077285:Rimonabant