Neurosteroids modulate nicotinic receptor function in mouse striatal and thalamic synaptosomes

J Neurochem. 1997 Jun;68(6):2412-23. doi: 10.1046/j.1471-4159.1997.68062412.x.


Progesterone and its A-ring reduced metabolites are allosteric activators of GABA(A) receptors. The studies reported here examined the effects of these steroids on brain nicotinic receptors using an 86Rb+ efflux assay that likely measures the function of alpha4beta2-type nicotinic receptors and [3H]dopamine release, which may be modulated by an alpha3-containing nicotinic receptor. Both of the A-ring reduced metabolites of progesterone were noncompetitive inhibitors of both assays, whereas progesterone inhibited only the 86Rb+ efflux assay. The 86Rb+ efflux assay was slightly more sensitive than was the dopamine release assay to steroid inhibition. Inhibition developed slowly for both assays (t1/2 = 0.4 min) and was reversed even more slowly (t1/2 = 10-15 min). Steroid addition did not alter either the rate of association of [3H]nicotine binding to brain membranes, nor was equilibrium binding changed. These findings argue that neurosteroids are allosteric inhibitors of brain nicotinic receptors.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5-alpha-Dihydroprogesterone
  • Allosteric Regulation
  • Animals
  • Anticonvulsants / pharmacology
  • Dopamine / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Mice
  • Mice, Inbred C3H
  • Neostriatum / cytology*
  • Nicotine / pharmacology
  • Nicotinic Agonists / pharmacology
  • Pregnanediones / chemistry
  • Pregnanediones / pharmacology
  • Pregnanolone / chemistry
  • Pregnanolone / pharmacology
  • Progesterone / metabolism
  • Progesterone / pharmacology*
  • Receptors, Nicotinic / chemistry
  • Receptors, Nicotinic / drug effects*
  • Rubidium Radioisotopes
  • Synaptosomes / chemistry*
  • Thalamus / cytology*
  • Tritium


  • Anticonvulsants
  • Nicotinic Agonists
  • Pregnanediones
  • Receptors, Nicotinic
  • Rubidium Radioisotopes
  • Tritium
  • Progesterone
  • Nicotine
  • 5-alpha-Dihydroprogesterone
  • Pregnanolone
  • Dopamine