title: Regulation of flunitrazepam binding in the dorsal horn of the spinal cord by adrenalectomy and corticosteroids.
abstract: Adrenal corticosteroids and adrenalectomy (ADX) have opposing effects on benzodiazepine binding sites in brain regions. These treatments were employed to study [3H]flunitrazepam (FLU) binding in regions punched out from the rat spinal cord. We found that binding was higher in dorsal horn than in ventral horn, and minimal in white matter. Clonazepam and RO 15-1788 largely displaced [3H]FLU binding, whereas RO 5-4864 was weakly active. Four days post-ADX, binding increased exclusively in the dorsal horn, and this effect was reversed by administration of corticosterone (CORT), but not dexamethasone (DEX) or aldosterone (ALDO) given over 4 days. When endogenous CORT was increased by administration of cold stress to adrenal-intact rats, reduced benzodiazepine (BDZ) binding was also observed in the dorsal horn. When added in vitro, only ALDO and not CORT or DEX, inhibited [3H]FLU binding. It is suggested that steroids with affinity for the type I corticosteroid receptor (CORT, ALDO) decrease [3H]FLU binding to a neural-type BDZ receptor in the dorsal horn. Reduction of the inhibitory BDZ system may be physiologically important, and can partly explain the enhancement of excitatory synaptic transmission produced by corticosteroids at the level of the spinal cord.
authors.affiliation: Laboratorio de Bioquímica Neuroendocrina, Instituto de Biología y Medicina Experimental, Buenos Aires, Argentina.
authors.forename: S L
authors.initials: SL
authors.lastname: González
authors.forename: M
authors.initials: M
authors.lastname: Ferrini
authors.forename: H
authors.initials: H
authors.lastname: Coirini
authors.forename: M C
authors.initials: MC
authors.lastname: González Deniselle
authors.forename: A F
authors.initials: AF
authors.lastname: De Nicola
mesh_terms: D000311:Adrenal Glands / Q000502:physiology*; D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D003900:Desoxycorticosterone / Q000031:analogs & derivatives / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D008901:Mineralocorticoids / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D008901:Mineralocorticoids; D011963:Receptors, GABA-A; D003900:Desoxycorticosterone; D000450:Aldosterone; C009413:tetrahydrodeoxycorticosterone; D005445:Flunitrazepam; D003907:Dexamethasone; D003345:Corticosterone