A possible central serotonergic mechanism involved in the effects of morphine on colonic motility in dog.

The effects of morphine (0.1 mg/kg) and 5-HTP (2 mg/kg) on colonic motility were investigated in dogs fasted for 15-22 h and fitted with two strain gauge transducers on the transverse colon at 8 and 12 cm from the ileo-colonic junction. The effects were compared to those obtained after previous intravenous (i.v.) (0.2 mg/kg) or intracerebroventricular (i.c.v.) (10 micrograms/kg) administration of methysergide. Morphine (0.1 mg/kg) increased the colonic motility index by 475% from 0 to 30 min, this primary transient stimulatory response being followed 30-40 min later by a secondary response lasting 3.2 +/- 0.5 h during which the motility index was also significantly increased. Intravenous injection of 5-HTP (1 mg/kg) produced a delayed (30-40 min) colonic hyperactivity with a 160% increase in the motility index from 1 to 3 h after injection similarly to the secondary response to morphine. This secondary colonic hyperactivity induced by morphine was blocked by both i.v. and i.c.v. methysergide administration--whereas the hyperactivity induced by 5-HTP was not blocked by previous i.v. or i.c.v. administration of methysergide--indicating that the similar effects of morphine and 5-HTP on colonic motility are not caused by the same mechanism. It was concluded that the long-lasting stimulatory effects of morphine on colonic motility in dog are centrally mediated and blocked at this level by 5-HT antagonists.