Increased behavioural response to intrathecal serotonin after lesion of serotonergic pathways with 5,7-dihydroxytryptamine seems not to be due to depletion of serotonin.

The behavioural response to intrathecal i.th. serotonin (5-HT) was examined in mice pretreated with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) or the 5-HT synthesis inhibitor p-chlorophenylalanine (PCPA) which produce similar extensive depletion of central 5-HT levels. Intrathecal 5-HT (0.4 micrograms) elicited a behavioural response consisting of reciprocal hindlimb scratching and biting or licking of the hindquarters indicative of nociceptive stimulation. The response to i.th. 5-HT was markedly increased 5 days after intracerebroventricular (i.c.v.) injection of 5,7-DHT (80 micrograms base per mouse). On the other hand, 24 h after the last pretreatment injection of PCPA (400 mg kg-1 for 6 consecutive days), the response to i.th. 5-HT was unaltered. These results indicate that i.c.v. 5,7-DHT produces supersensitivity to 5-HT. Since PCPA failed to alter the effect of 5-HT, the supersensitivity seems not to be due to depletion of 5-HT levels after the lesion.