Possible involvement of supraspinal opioid and GABA receptors in CDP-choline-induced antinociception in acute pain models in rats

Hamurtekin E., Bagdas D., Gurun M. S.

NEUROSCIENCE LETTERS, vol.420, no.2, pp.116-121, 2007 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 420 Issue: 2
  • Publication Date: 2007
  • Doi Number: 10.1016/j.neulet.2007.04.058
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.116-121
  • Bursa Uludag University Affiliated: Yes


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 CDPcholine 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 mu mol) produced dose-dependent antinociception. Non-specific opioid receptor antagonist naloxone (10 mu g; i.c.v.) and GABA(B) receptor antagonist CGP-35348 (20 mu g; i.c.v.) pretreatments inhibited the antinociceptive effects of CDP-choline (1.0 mu mol; i.c.v.). In contrast, the alpha-1 adrenergic receptor antagonist prazosin (20 mu g; i.c.v.), alpha-2 adrenergic receptor antagonist yohimbine (30 mu g; i.c.v.) and non-specific scrotonin receptor antagonist methysergide (20 mu g; 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 GABAB 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. (c) 2007 Elsevier Ireland Ltd. All rights reserved.