Intrathecal DSP4 selectively depletes spinal noradrenaline and attenuates morphine analgesia.

The noradrenergic neurotoxin DSP4 was injected intrathecally into the lumbar spinal subarachnoid space of the rat. After 10 days, dose-response curves for tail-flick inhibition were determined for both intraperitoneal and intraventricular injections of morphine. In rats pretreated with DSP4, the analgesic effect of morphine given either intraventricularly or intraperitoneally was significantly attenuated. The noradrenaline and 5-hydroxytryptamine contents in the brain-stem and the spinal cord were also measured. Intrathecal DSP4 depleted noradrenaline in the spinal cord but not in the brain-stem. Neither brain-stem or spinal cord 5-hydroxytryptamine was affected by DSP4.