Systemic morphine produce antinociception mediated by spinal 5-HT7, but not 5-HT1A and 5-HT2 receptors in the spinal cord

Background and purpose: The serotonergic system within the spinal cord have been proposed to play an important role in the analgesic effects of systemic morphine. Currently, seven groups of 5-HT receptors (5-HT1-7) have been characterized. One of the most recently identified subtypes of 5 HT receptor is the 5-HT7 receptor. We aimed to examine the role of spinal 5-HT7 receptors in the antinociceptive effects of systemic morphine. Experimental approach: The involvement of spinal 5-HT7 receptor in systemic morphine antinociception was compared to that of the 5-HT1A and 5-HT2 receptors by using the selective 5-HT7 receptor antagonist, SB-269970, the selective 5-HT1A receptor antagonist, WAY 100635, the selective 5-HT2 antagonist ketanserin as well as the non-selective 5-HT1,(2),(7) receptor antagonist, metergoline. Nociception was evaluated by the radiant heat tail-flick test. Key results: I.t. administration of SB-269970 (10 mu g) and metergoline (20 mg) completely blocked the s.c. administered morphine-induced (1, 3, 5 and 10mgkg(-1)) antinociception in a time-dependent manner. Additionally, i.t. administration of SB-269970 (1, 3, 10 and 20 mg) and metergoline (1, 5, 10 and 20 mg) dose dependently inhibited the antinociceptive effects of a maximal dose of morphine (10mg kg(-1), s.c.). I.t. administration of WAY 100635 (20 mg) or ketanserine (20 mg) did not alter morphine-induced (1, 3, 5 and 10mg kg(-1), s.c.) antinociception. Conclusion and implications: These findings indicate that the involvement of spinal 5-HT7, but not of 5-HT1A or of 5-HT2 receptors in the antinociceptive effects of systemic morphine.