Elsevier

Life Sciences

Volume 28, Issue 21, 21 May 1981, Pages 2343-2347
Life Sciences

Differential ontogeny of Type 1 and Type 2 benzodiazepine receptors

https://doi.org/10.1016/0024-3205(81)90498-7Get rights and content

Abstract

The postnatal development of Type 1 and Type 2 benzodiazepine receptors in rat cerebral cortex was studied using CL 218,872, a novel triazolopyridazine. On postnatal day 1 most 3H-flunitrazepam binding sites appeared to be Type 2 receptors, which increased rapidly during the first week of life and reached adult levels by 3–4 weeks of age. Type 1 receptors, on the other hand, represented only a small percentage of the binding sites on postnatal day 1 and did not begin to increase in number until approximately 7–16 days of age. These results demonstrate a differential postnatal development of two sub-populations of benzodiazepine receptors.

References (20)

  • H.B. Bosmann et al.

    FEBS Lett.

    (1978)
  • R. Speth et al.

    Life Sci.

    (1978)
  • A.S. Lippa et al.

    Pharmac. Biochem. Behav.

    (1979)
  • P. Skolnick et al.

    Pharmac. Biochem. Behav.

    (1979)
  • A.S. Lippa et al.

    Pharmac. Biochem. Behav.

    (1979)
  • C.A. Klepner et al.

    Pharmac. Biochem. Behav.

    (1979)
  • C. Braestrup et al.

    Brain Res.

    (1978)
  • J.M. Palacios et al.

    Brain Res.

    (1979)
  • P. Mallorga et al.

    Neuropharmacol.

    (1980)
  • O.H. Lowry et al.

    J. Biol. Chem.

    (1951)
There are more references available in the full text version of this article.

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