Increased behavioural response to intrathecal substance P after intracerebroventricular 5,7-dihydroxytryptamine but not after p-chlorophenylalanine administration.

The behavioural response to intrathecally injected substance P (SP, 1.25 ng) was investigated in mice after lesioning of serotonergic (5-HT) pathways by intracerebroventricular 5,7-dihydroxytryptamine (5,7-DHT, 80 micrograms base/mouse) and after 5-HT synthesis inhibition by p-chlorophenylalanine (PCPA, 400 mg kg-1 for 6 consecutive days). Pretreatment with 5,7-DHT and PCPA reduced the 5-HT level in the spinal cord to 6 and 7% of controls and the noradenaline (NA) level to 69 and 84% of controls, respectively. Intrathecally injected SP produced a response consisting of vigorous biting, licking and scratching of the caudal part of the body. The response to SP was significantly increased 5 days after injection of 5,7-DHT, but only a non-significant tendency towards enhancement of the response was found after 24 h. There was no change in the response to SP 24 h after the last injection of PCPA. It is suggested that 5,7-DHT but not PCPA induces receptor supersensitivity to SP, and that reduction in spinal SP by 5,7-DHT may be a factor in this change in receptor sensitivity.