Characterization of stress-induced alterations in [3H] Ro5-4864 binding to peripheral benzodiazepine receptors in rat heart and kidney.
Inescapable tailshock has been shown to elicit a tissue specific decrease in the density of peripheral benzodiazepine receptors (PBR). We have now explored possible mechanisms that may be responsible for this phenomenon. An 80 minute session of inescapable tailshock produced a reduction in the binding of [3H] Ro5-4864 to renal membranes at 0, 1 and 2 hr after stress, with values returning to control (naive) levels within 24 hr. In cardiac membranes, statistically significant reductions were observed only at 2 and 4 hr after stress. The role of the pituitary-adrenal axis and the sympathetic nervous system in this phenomenon was assessed by subjecting adrenalectomized, hypophysectomized, 6-OHDA-treated or control (sham-operated or saline-treated) rats to inescapable shock. Neither adrenalectomy, hypophysectomy, nor 6-OHDA pretreatment altered the stress-induced reduction in renal PBR. However, the stress-induced decrease in renal PBR was blocked by pretreatment with clonazepam (1 mg/kg), a potent anxiolytic with low affinity for PBR.
Drugan
R C
RC
Clinical Neuroscience Branch, NIMH, Bethesda, MD 20892.
Basile
A S
AS
Crawley
J N
JN
Paul
S M
SM
Skolnick
P
P
D000315:Adrenalectomy; D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism*; D002998:Clonazepam / Q000494:pharmacology; D003292:Convulsants / Q000378:metabolism*; D004597:Electroshock; D007016:Hypophysectomy; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D013315:Stress, Psychological / Q000378:metabolism*
D001570:Benzodiazepinones; D003292:Convulsants; D011963:Receptors, GABA-A; C028513:4'-chlorodiazepam; D002998:Clonazepam