Is upregulation of benzodiazepine receptors a compensatory reaction to reduced GABAergic tone in the brain of stressed mice?
Effects of various forms of stress on the GABAA receptor-chloride ionophore complex in the brain of NMRI mice were investigated. Male albino mice were subjected to stress by placing them on small platforms (SP; 3.5 cm diameter) surrounded by water for 24 h. This experimental model contains several stress factors like rapid eye movement (REM) sleep deprivation, isolation, immobilization, falling into water and soaking. As additional stress control groups we used animals subjected to isolation, large platform (9.0 cm diameter) and repeated swimming stress. SP stress induced an increase in the number of cortical benzodiazepine (BDZ) receptors and a reduction in the GABA-stimulated 36Cl-uptake by brain microsacs, whereas none of these changes could be observed in animals exposed to isolation, swimming or large platform stresses. Furthermore, the amount of GABA-induced stimulation of [3H]flunitrazepam binding was reduced in cortical brain membranes of SP-stressed animals, an effect due to fact that these animals displayed an increase in the basal [3H]flunitrazepam binding, whereas the absolute level of maximally enhanced BDZ binding in the presence of GABA did not differ from those found in controls. Neither basal [3H]muscimol binding or thiopentone sodium-induced stimulation of [3H]flunitrazepam binding were changed in any group of stressed mice. It is proposed that the observed upregulation in the number (Bmax) of cortical BDZ receptors in SP-stressed mice may represent a compensatory response to a stress-induced attenuation of GABAergic neurotransmission.
Pokk
P
P
Department of Pharmacology, University of Tartu, Estonia.
Kivastik
T
T
Sobol
D
D
Liljequist
S
S
Zharkovsky
A
A
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D008297:Male; D051379:Mice; D009118:Muscimol / Q000378:metabolism; D011963:Receptors, GABA-A / Q000032:analysis*; D013312:Stress, Physiological / Q000378:metabolism*; D013874:Thiopental / Q000494:pharmacology; D015854:Up-Regulation; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D002712:Chlorides; D011963:Receptors, GABA-A; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; D013874:Thiopental