Test-dependent antinociceptive effect of spinal serotonin release induced by intrathecal p-chloroamphetamine in mice

The effect of direct intrathecal injection of p-chloroamphetamine (PCA) into the lumbar subarachnoid space was investigated in mice. PCA (0.6 - 20 micrograms) induced a dose-related prolongation of response latencies in the tail-flick test, but failed to affect the hind-paw lick response in a hot-plate test employing slowly rising temperature. PCA (5 micrograms) given intracerebroventricularly did, however, significantly elevate the response temperature in the hot-plate test. The antinociceptive effect of PCA in the tail-flick test was prevented by spinalization, by pretreatment with the selective serotonergic re-uptake blocker zimelidine (20 mg X kg-1 i.p.) and by the serotonin synthesis inhibitor p-chlorophenylalanine (300 + 300 + 150 mg X kg-1 i.p. 72, 48 and 24 h before test). It is concluded that PCA given intrathecally releases serotonin from spinal terminals, which may under certain conditions induce antinociception.