DEVELOPMENTAL REGULATION OF 5-HT2 AND 5-HT1C MESSENGER-RNA AND RECEPTOR LEVELS

We investigated the regulation of 5-HT2 and 5-HT1C receptors and their corresponding mRNAs during rat brain development. This study showed that 5-HT2 and 5-HT1C receptors increased markedly during ontogeny. 5-HT2 receptors, measured with [H-3]ketanserin or [I-125]lysergic acid diethylamide binding, increased 8-fold between embryonic day 17 (E17) and postnatal day 13 (P13). 5-HT2 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-HT2 receptor and mRNA expression appeared to correlate with the serotonergic hyperinnervation of the cortex which occurs between P2 and P17. 5-HT1C receptors, measured with [I-125]lysergic acid diethylamide under site-specific conditions, increased 2-fold between E17 and P27. 5-HT1C mRNA increased 5-fold between E17 and P27. Interestingly, the developmentally induced variations in 5-HT1C 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.