Increased sensitivity to intrathecal substance P following chronic administration of zimelidine

The behavioural response to intrathecal substance P (SP) was evaluated following acute and chronic administration of the selective serotonin reuptake inhibitor zimelidine. A single dose of zimelidine (10 mg/kg) attenuated the response to SP by approximately 40%, in agreement with previous findings that acute administration of zimelidine reduces nociceptive behaviour. Twenty-four hours following the withdrawal of long-term treatment with zimelidine (10 mg/kg X 2 daily for 14 days) the behavioural response to SP was increased by 116%. This may indicate the development of supersensitivity to SP, or may reflect an increased responsiveness to noxious stimuli due to reduced serotonergic inhibition.