title: Possible involvement of supraspinal opioid and GABA receptors in CDP-choline-induced antinociception in acute pain models in rats.
abstract: Cytidine-5'-diphosphate choline (CDP-choline; citicoline) is an essential endogenous compound normally produced by the organism and is a source of cytidine and choline. Our recent studies on acute pain models demonstrate that intracerebroventricularly administered CDP-choline produces antinociception via supraspinal alpha-7 nicotinic acetylcholine receptors-mediated mechanism in rats. However, it remains to be elucidated which other supraspinal mechanisms are involved in the antinociceptive effect of CDP-choline. In this study, we investigated the role of the supraspinal opioidergic, GABAergic, alpha-adrenergic and serotonergic receptors in CDP-choline-induced antinociception. The antinociceptive effect of CDP-choline was evoked by the intracerebroventricular (i.c.v.) administration. Two different pain models were utilized: thermal paw withdrawal test and mechanical paw pressure test. The i.c.v. administration of CDP-choline (0.5, 1.0 and 2.0 micromol) produced dose-dependent antinociception. Non-specific opioid receptor antagonist naloxone (10 microg; i.c.v.) and GABA(B) receptor antagonist CGP-35348 (20 microg; i.c.v.) pretreatments inhibited the antinociceptive effects of CDP-choline (1.0 micromol; i.c.v.). In contrast, the alpha-1 adrenergic receptor antagonist prazosin (20 microg; i.c.v.), alpha-2 adrenergic receptor antagonist yohimbine (30 microg; i.c.v.) and non-specific serotonin receptor antagonist methysergide (20 microg; i.c.v.) pretreatments had no effect on CDP-choline-induced antinociception in the thermal paw withdrawal test and in the mechanical paw pressure test. Therefore, it can be postulated that i.c.v. administered CDP-choline exerts antinociceptive effect mediated by supraspinal opioid and GABA(B) receptors in acute pain models. Furthermore, supraspinal alpha-adrenergic and serotonergic receptors do not appear to be involved in the antinociceptive effect of CDP-choline.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Uludag University, 16059 Görükle, Bursa, Turkey.
authors.forename: Emre
authors.initials: E
authors.lastname: Hamurtekin
authors.forename: Deniz
authors.initials: D
authors.lastname: Bagdas
authors.forename: M Sibel
authors.initials: MS
authors.lastname: Gurun
mesh_terms: D000208:Acute Disease / Q000628:therapy; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003566:Cytidine Diphosphate Choline / Q000494:pharmacology*; D004195:Disease Models, Animal; D004525:Efferent Pathways / Q000187:drug effects / Q000378:metabolism; D018756:GABA Antagonists / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D018079:Receptors, GABA / Q000187:drug effects / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000187:drug effects / Q000378:metabolism; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D000700:Analgesics; D018756:GABA Antagonists; D009292:Narcotic Antagonists; D011942:Receptors, Adrenergic, alpha; D018079:Receptors, GABA; D018080:Receptors, GABA-B; D011957:Receptors, Opioid; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D003566:Cytidine Diphosphate Choline