Role of serotonin in the regulation of β-adrenoceptors by antidepressants

The role of serotonin (5-HT) in the regulation of the β-receptor density induced by long-term treatment with typical and atypical antidepressants was examined. Treatment with either mianserin (15 mg/kg, twice daily) or maprotiline (10 mg/kg, twice daily) for 7 days caused a significant decrease in the β-receptor density, measured 6 h after the last dose, without a change in affinity. The reduction in β-receptors disappeared rapidly (within 24 h). However, treatment with mianserin or maprotiline combined with fluoxetine, a selective 5-HT uptake inhibitor, significantly decreased the β-receptor density even 24 h after the last dose. The combined administration of mianserin and 5-hydroxytryptophan (5-HTP) mimicked the effect of the combination with fluoxetine. Following pretreatment with p-chlorophenylalanine (PCPA) for 6 days, desipramine treatment for 3 days significantly decreased the β-receptors 6 h after the last dose but this desipramine-induced decrease in β-receptors was rapidly reversible (within 24 h). These results demonstrates that while intrasyneptic 5-HT levels are not a factor in the decrease in β-receptors they do play an important role in the preservation of the down-regulated state of the β-receptor caused by antidepressants from rapid reversibility.