Developmental and Synaptic Regulation of 5-HT₂ and 5-HT_1c Serotonin Receptors

Summary

5-HT₂ and 5-HT_1c receptors are regulated by a number of exogenous and endogenous factors via biochemical and molecular mechanisms which remain largely uncharacterized. To clarify some of these we investigated the effects of (1) normal perinatal development and (2) acute and chronic receptor blockade on the levels of 5-HT₂ and 5-HT_1c receptor binding and mRNAs. During rat brain development, 5-HT₂ receptors increased 8-fold while 5-HT₂ receptor mRNA rise by 13-fold. 5-HT_1c receptors displayed a 2.2-fold elevation while 5-HT_1c mRNA increased 6-fold. On the basis of these observations, we postulate that transcriptional processes appear to be important for regulating 5-HT₂ receptors during development.

Mianserin, administered i.p. for 4, 10 or 21 days caused a 50–70% decrease in brain levels of 5-HT₂ and 5-HT_1c receptors as assessed by quantitative receptor autoradiography or radioligand binding. A small increase in 5-HT_1c receptor mRNA (20–25%) was seen after 10 and 21 days of continuous mianserin treatment while 5-HT₂ receptor mRNA levels were unchanged. These results indicate that mianserin decreases 5-HT₂ and 5-HT_1c receptors without altering steady-state mRNA levels.