Developmental regulation of 5-HT 2 and 5-HT 1C mRNA and receptor levels

Abstract

We investigated the regulation of 5-HT 2 and 5-HT 1C receptors and their corresponding mRNAs during rat brain development. This study showed that 5-HT 2 and 5-HT 1C, receptors increased markedly during ontogeny. 5-HT 2 receptors, measured with [ 3H]ketanserin or [ 125I]lysergic acid diethylamide binding, increased 8-fold between embryonic day 17 (E17) and postnatal day 13 (P13). 5-HT 2 receptor mRNA levels, quantified by probing Northern blots of total RNA with a synthetic oligonucleotide cDNA probe, multiplied 13-fold between E17 and P5. The developmental pattern of 5-HT 2 receptor and mRNA expression appeared to correlate with the serotonergic hyperinnervation of the cortex which occurs between P2 and P17. 5-HT 1C receptors, measured with [ 125I]lysergic acid diethylamide under site-specific conditions, increased 2-fold between E17 and P27. 5-HT 1C mRNA increased 5-fold between E17 and P27. Interestingly, the developmentally induced variations in 5-HT 1C receptors did not precisely correlate with mRNA alterations. Further study of the factors responsible for these alterations could help to explain the molecular and biochemical mechanisms responsible for modulating receptor levels in vivo.