Central- and peripheral-type benzodiazepine receptors: similar regulation by stress and GABA receptor agonists.
Central- and peripheral-type benzodiazepine (BD) receptors were labelled either by 3H-flunitrazepam or 3H-Ro 5-4864 in vitro after stress and in vivo administration of GABAA and GABAB agonists. A significant increase in the density of cerebral cortex and kidney BD binding sites was observed in rats after forced swimming stress. Similar changes in both type of BD receptors were also followed when naive (stressed) and handling-habituated (unstressed) rats were used. Stress in both models was unable to change the affinity of BD receptors in cerebral cortex, but significantly lowered it in kidneys. Acute treatment of rats with muscimol (1.5 mg/kg) or (-)baclofen (5 mg/kg) resulted in marked increase in the affinity of BD binding not only in cerebral cortex but also in kidneys. After (-)baclofen treatment the number of BD binding sites was lowered in the structures studied. In a separate study mice selected according to their behavioral response to (-)baclofen (1 mg/kg) were studied. Two weeks after the selection it appeared that baclofen responders were behaviorally more "anxious" than baclofen nonresponders. The number of BD binding sites was reduced in cerebral cortex, cerebellum, heart and kidneys in baclofen responders as compared to baclofen nonresponders. In several cases the changes in peripheral BD binding sites were even more pronounced than those in central ones. The data presented here evidence that peripheral- and central-type BD receptors are regulated similarly by GABA and some models of stress. The physiological mechanisms involved in similar regulation of central- and peripheral-type BD receptors are yet unknown.
Rägo
L
L
Department of Pharmacology, Tartu University, Estonia, USSR.
Kiivet
R A
RA
Harro
J
J
Pŏld
M
M
D000818:Animals; D001007:Anxiety / Q000503:physiopathology; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001570:Benzodiazepinones / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D005445:Flunitrazepam / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D009118:Muscimol / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000032:analysis / Q000187:drug effects / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D001570:Benzodiazepinones; D011963:Receptors, GABA-A; D009118:Muscimol; C028513:4'-chlorodiazepam; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D001418:Baclofen