The antinociceptive effects of centrally administered CDP-choline on acute pain models in rats: the involvement of cholinergic system.
This study investigates the antinociceptive effect of intracerebroventricular (i.c.v.) injection of cytidine-5'-diphosphate choline (CDP-choline; citicoline) and the involvement of cholinergic mechanisms in rats. Three different pain models were utilized: thermal paw withdrawal test, mechanical paw pressure test and acetic acid writhing test. The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 micromol) produced dose and time-dependent antinociception. Equimolar dose of choline (1 micromol; i.c.v.) produced antinociceptive response similar to the one observed in CDP-choline given animals. On the other hand, cytidine (1 micromol; i.c.v.) failed to produce response in the thermal paw withdrawal test and the mechanical paw pressure test but in the writhing test in which it produced significant antinociceptive effect. CDP-choline-induced antinociception was prevented by the neuronal high affinity choline uptake inhibitor HC-3 (1 microg; i.c.v.), the nonselective nicotinic receptor antagonist mecamylamine (50 microg; i.c.v.) and by the alpha(7)-selective nicotinic receptor antagonist, MLA (25 microg; i.c.v.). However, it was not changed by the nonselective muscarinic receptor antagonist atropine (10 microg; i.c.v.) in the thermal paw withdrawal test and mechanical paw pressure test. In the writhing test, all antagonist pretreatments produced blockade similar to that obtained from CDP-choline injected animals. CDP-choline did not impair the motor performance of rats as evaluated by a rota-rod test. Therefore, it can be postulated that CDP-choline exerts an antinociceptive effect mediated by a central cholinergic mechanism. Activation of specific alpha(7)-nicotinic cholinergic receptors through the activation of presynaptic cholinergic mechanisms appears to be involved in the antinociceptive effect of this drug.
Hamurtekin
Emre
E
Uludag University, Faculty of Medicine, Department of Pharmacology and Clinical Pharmacology, 16059, Görükle, Bursa, Turkey.
Gurun
M Sibel
MS
D000109:Acetylcholine / Q000378:metabolism*; D000208:Acute Disease; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000378:metabolism; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D000700:Analgesics; C579165:Chrna7 protein, rat; D014179:Neurotransmitter Uptake Inhibitors; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D003566:Cytidine Diphosphate Choline; D000109:Acetylcholine