The effects of chronic treatment with the 5-hydroxytryptamine uptake blocker zimelidine on central 5-hydroxytryptamine mechanisms. Evidence for the induction of a low affinity binding site for 5-hydroxytryptamine.

Male rats were treated with saline or the 5-hydroxytryptamine (5-HT) uptake inhibitor zimelidine (10 mumol/kg postoperatively) twice daily for a period of 14 days. The effects of this treatment on [5-3H]HT binding in the cerebral cortex and hypothalamus and on 5-HT synthesis were examined. Long-term treatment with zimelidine induced a low affinity site for 5-HT (Kd approximately 20 nM) in both areas and a reduced number of high affinity binding sites in the hypothalamus. Long-term zimelidine treatment did not attenuate the feed-back mediated inhibition of 5-HT synthesis. These findings suggest that chronic zimelidine treatment could result in a reduced activity at postsynaptic 5-HT receptor sites.