The effect of lowering the 5-hydroxytryptamine content of the rat spinal cord on analgesia produced by morphine.

1. Injection of 5,6-dihydroxytryptamine (5,6-DHT, 50 mug) into a lateral cerebral ventricle of male rats lowered the 5-hydroxytryptamine (5-HT) content of the lumbar cord to 12.8% and reduced the analgesic effect of low doses of morphine (0.64-1.63 mg/kg), tested by exerting pressure on the foot; after doses of morphine of 1.33-1.63 mg/kg, the analgesic response was reduced or abolished in 33% of the rats, and after 0.64 mg/kg, 58% of the animals failed to respond normally.2. Two days after an I.P. injection of p-chlorophenylalanine (pCPA, 320 mg/kg), the loss of analgesic potency of morphine was more pronounced than after intraventricular 5,6-HDT. The 5-HT content was lowered to about 8% in the lumbar cord, and to 20% or less in pons and medulla.3. The experiments show that interference with the descending tryptaminergic axons innervating the cord is by itself sufficient to reduce analgesia due to morphine, but they do not exclude the possibility that other tryptaminergic neurones take part in the effect of pCPA. The contribution to the analgesic effect of morphine made by the interaction of tryptaminergic axons with the interneurones ;gating' the afferent impulses in the posterior columns is discussed.