2P432 Spinally mediated behavioural response induced by intrathecal morphine-3-glucuronide in mice

Intrathecal (i. t. ) administration of morphine-3-glucuronide (M3G), a major metabolite of morphine, produced a severe hindlimb scratching followed by biting and licking in mice. The present study was undertaken to examine the involvement of the tachykinin NK1 and NK2 receptors on the behavioural response evoked by i. t. administration of M3G. These characteristic behavioural responses were dose-dependently inhibited by i, t. co-administration of tachykinin NK1 receptor antagonists, sendide, CP-99,994 and RP-67580. A significant antagonistic effect of i. t. administered [D-Phe7, D-His9]substanceP (SP) (6-11), a selective antagonist for SP receptors, was observed against the M3G-induced behaviours. The NK 2 receptor antagonist MEN-10376 given i, t. produced no inhibitory effect on M3G-induced behaviour. The present results suggest that SP-containing neurones in the spinal cord may be involved in elicitation of the behavioural response following i. t, injection of M3G.