Modulation of benzodiazepine receptor binding in mouse brain by adrenalectomy and steroid replacement.
Adrenal steroids alter neuronal excitability in the central nervous system (CNS), and evidence from in vitro studies indicates that at least some of these effects are mediated by the GABAergic system. Benzodiazepine receptor binding, among other sites on the GABA complex, has been implicated in steroid-induced alterations in the CNS. To investigate the modulation of benzodiazepine receptor binding by adrenal steroids, we examined receptor binding determined by an in vivo technique in mice after adrenalectomy, hypophysectomy and after replacement with several naturally occurring and synthetic steroids. Benzodiazepine receptor binding was substantially augmented in cortex, hypothalamus, and hippocampus in mice 1 week after adrenalectomy, and these increases appeared to be due to increased receptor number rather than changes in apparent affinity. Similar results in cortex were found after hypophysectomy. Replacement with physiologic, but not lower doses, of corticosterone reversed the changes induced by adrenalectomy. Chronic treatment with deoxycorticosterone also returned binding to control values, but chronic administration with dexamethasone, aldosterone and dihydroprogesterone did not alter binding after adrenalectomy. Adrenalectomy did not alter non-specific binding or GABA concentrations in cortex, and delivery of radioligand did not appear to be affected. These results indicate that adrenal steroids modulate benzodiazepine receptor binding in vivo, perhaps via the CR subtype of corticosteroid receptors. The steroid-benzodiazepine interaction may be especially important in the stress response.
Miller
L G
LG
Department of Psychiatry, Tufts-New England Medical Center, Boston, MA.
Greenblatt
D J
DJ
Barnhill
J G
JG
Thompson
M L
ML
Shaderh
R I
RI
D004092:20-alpha-Dihydroprogesterone / Q000494:pharmacology*; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003345:Corticosterone / Q000494:pharmacology*; D003900:Desoxycorticosterone / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D007016:Hypophysectomy; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011374:Progesterone / Q000031:analogs & derivatives*; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values
D011963:Receptors, GABA-A; D004092:20-alpha-Dihydroprogesterone; D003900:Desoxycorticosterone; D000450:Aldosterone; D011374:Progesterone; D003907:Dexamethasone; D003345:Corticosterone