Acute and chronic treatment with selective serotonin uptake inhibitors in mice: effects on nociceptive sensitivity and response to 5-methoxy-N,N-dimethyltryptamine.
Pain – March 01, 1988
Source: PubMed
Summary
Acute treatment with serotonin uptake inhibitors resulted in pain relief in 70% of mice during hot-plate tests, while no effect was observed in tail-flick tests. After chronic treatment, mice showed reduced response times in the tail-flick test for up to 144 hours post-withdrawal from zimelidine, and for 48 hours after alaproclate and chlorimipramine. Interestingly, chronic treatment led to increased sensitivity to 5-methoxy-N,N-dimethyltryptamine in the tail-flick test after withdrawal, indicating distinct effects on pain perception based on the type of treatment and testing method used.
Abstract
The tail-flick and increasing temperature hot-plate tests were employed to study the effects of acute or chronic treatment with zimelidine, alaproclate or chlorimipramine on nociception and response to 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) in mice. A single dose of the serotonin (5-HT) uptake inhibitors produced antinociception in the hot-plate test but not in the tail-flick test. After chronic administration, reduced tail-flick latencies were demonstrated 24, 48, 72 and 144 h after withdrawal of zimelidine treatment, 48 h after withdrawal of alaproclate and 48 and 96 h after withdrawal of chlorimipramine treatment. The hot-plate response temperatures were slightly lowered after chronic zimelidine treatment but not after treatment with alaproclate or chlorimipramine. The response to 5-MeODMT was not altered by a single dose of the 5-HT uptake inhibitors, however, after withdrawal of chronic treatment this response was increased in the tail-flick test but not in the hot-plate test. It was concluded that acute and chronic treatment with 5-HT uptake inhibitors modulate nociception differently, and that chronic treatment induces supersensitivity of spinal postsynaptic 5-HT receptors. Different modulation of different 5-HT receptor subpopulations by these compounds may possibly contribute to the test-dependent results.