Increase in locomotor activity after acute administration of the nicotinic receptor agonist 3-bromocytisine in rats.
Nicotinic acetylcholine receptors influence striatal dopaminergic activity and its outcome on motor behavior. For these reasons, nicotinic receptors have been considered as therapeutically relevant targets for Parkinson's disease, in which a dramatic loss of dopamine affects motor functions. The aim of the present work was to compare the effects on locomotor activity induced by the nicotinic agonist cytisine and two brominated derivatives, 5- and 3-bromocytisine (5-BrCy and 3-BrCy) using nicotine for comparison. After acute systemic administration of the agonists only 3-BrCy induced an increase in locomotor activity. To study the mechanism of action involved in this increase we co-administered 3-BrCy with the nicotinic antagonist mecamylamine and also examined 3-BrCy's effects in rats pre-treated with the long acting nicotinic antagonist chlorisondamine, administered directly in the dorsal and ventral striatum. We studied the role of the dopaminergic system by co-administration of the D2 dopamine receptor antagonist, haloperidol. The results indicate that the increase in motor activity elicited by 3-BrCy was mediated by nicotinic receptors in the dorsal and ventral striatum and depends on the interaction of nicotinic receptors with the dopaminergic system. We conclude that 3-BrCy might be a new tool to study the modulation of the dopaminergic system by nicotinic receptors and their behavioral implications.
Abin-Carriquiry
Juan Andrés
JA
Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. abin@adinet.com.uy
Urbanavicius
Jessika
J
Scorza
Cecilia
C
Rebolledo-Fuentes
Marcos
M
Wonnacott
Susan
S
Cassels
Bruce K
BK
Dajas
Federico
F
D000470:Alkaloids / Q000008:administration & dosage*; D000818:Animals; D001952:Bridged-Ring Compounds / Q000008:administration & dosage*; D002714:Chlorisondamine / Q000008:administration & dosage; D004334:Drug Administration Schedule; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D011807:Quinolizines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001952:Bridged-Ring Compounds; D002714:Chlorisondamine; D018722:Nicotinic Agonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; C438730:3-bromocytisine; D000093843:Quinolizidine Alkaloids