Acute and chronic treatment with selective serotonin uptake inhibitors in mice: effects on nociceptive sensitivity and response to 5-methoxy-N,N-dimethyltryptamine.

Acute doses of serotonin-uptake inhibitors (zimelidine, alaproclate, chlorimipramine) produced pain relief in mice on the hot-plate test but not the tail-flick test. After chronic treatment and withdrawal, tail-flick latencies shortened—indicating increased pain sensitivity—at multiple time points for each drug. Hot-plate response temperatures were slightly lowered only after chronic zimelidine. The drugs did not alter the response to a serotonin-receptor agonist after a single dose, but after withdrawal of chronic treatment, the response increased in the tail-flick test only. The authors conclude that acute and chronic treatment with these drugs modulate pain differently, and that chronic treatment leads to supersensitivity of spinal serotonin receptors, with test-dependent effects possibly due to different serotonin-receptor subtypes.

Study at a glance

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.