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.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004347:Drug Interactions; D007278:Injections, Spinal; D051379:Mice; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D013373:Substance P / Q000494:pharmacology*; D015031:Zimeldine / Q000494:pharmacology*
D013373:Substance P; D015031:Zimeldine