Research report
Developmental regulation of 5-HT2 and 5-HT1C mRNA and receptor levels

https://doi.org/10.1016/0165-3806(91)90236-CGet rights and content

Abstract

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 [3H]ketanserin or [125I]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 [125I]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.

References (44)

  • G. Milligan et al.

    Development of opiate receptors and GTP-binding regulatory proteins in neontal rat brain

    J. Biol. Chem.

    (1987)
  • P.J. Munson et al.

    LIGAND: a versatile computerized approach for characterization of ligand binding systems

    Anal. Biochem.

    (1980)
  • A. Pazos et al.

    Quantitative autoradiographic mapping of serotonin receptors in rat brain. II. Serotonin-2 receptors

    Brain Res.

    (1985)
  • B.L. Roth et al.

    The postnatal development of VIP binding sites in rat forebrain and hindbrain

    Peptides

    (1985)
  • B.L. Roth et al.

    Minireview: multiple mechanisms of serotonergic signal transduction

    Life Sci.

    (1987)
  • B.L. Roth et al.

    The effects of morphine on catecholamine metabolism during development

    Brain Res.

    (1980)
  • J.W. Spain et al.

    Ontogeny of benzomorphan-selective (kappa) sites: a computerized analysis

    Life Sci.

    (1983)
  • J.A. Wallace et al.

    Development of the serotonergic system in the rat embryo: an immunohistochemical study

    Brain Res. Bull.

    (1983)
  • M. Wohltmann et al.

    Differential postnatal development of mu and delta opiate receptors

    Dev. Brain Res.

    (1982)
  • N. Brunello et al.

    Different synaptic location of mianserin and imipramine binding sites

    Science

    (1982)
  • J.M. Chirgwin et al.

    Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

    Biochemistry

    (1979)
  • R.J. D'Amato et al.

    Ontogeny of the serotonergic projection to rat neocortex: transient expression of a dense innervation to primary sensory areas

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    Present address: Geriatic Research and Education Clinical Center, Department of Psychiatry, University of Washington Medical School, Seattle, WA, U.S.A.

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