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

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 μmol) produced dose-dependent antinociception. Non-specific opioid receptor antagonist naloxone (10 μg; i.c.v.) and GABAB receptor antagonist CGP-35348 (20 μg; i.c.v.) pretreatments inhibited the antinociceptive effects of CDP-choline (1.0 μmol; i.c.v.). In contrast, the alpha-1 adrenergic receptor antagonist prazosin (20 μg; i.c.v.), alpha-2 adrenergic receptor antagonist yohimbine (30 μg; i.c.v.) and non-specific serotonin receptor antagonist methysergide (20 μg; 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.