The effect of foot-
shock stress on t-[35S]butylbicyclophosphorothionate [( 35S]
TBPS) binding to fresh unwashed membrane preparations from rat cerebral cortex was studied and was compared to those of GABAA receptor agonists and antagonists and to positive and negative modulators of the GABAergic transmission. [35S]
TBPS binding was increased in the cerebral cortex of rats exposed to foot
shock compared to that of nonstressed rats. Scatchard analysis revealed that the effect of foot
shock was due to an increase in the total number of [35S]
TBPS binding sites. In contrast, the in vitro addition of
muscimol or
GABA induced a dose-dependent inhibition of [35S]
TBPS binding, an effect abolished by the concomitant addition of the
GABA receptor antagonist,
bicuculline, which, per se, enhanced [35S]
TBPS binding by 73%. Thus,
bicuculline, similar to stress, increased [35S]
TBPS binding in the same membrane preparation. In contrast to stress, the
anxiolytic and positive modulators of the GABAergic transmission (
ZK 93423,
ZK 91296, and
diazepam) inhibited the specific binding of [35S]
TBPS in a concentration-dependent manner. The greatest inhibitory effect was produced by
ZK 93423 at 30 microM (31% of control), followed by
diazepam (54% of control) and by the partial agonist
ZK 91296 (61% of control). Scatchard plot analysis indicated that the inhibition induced by
ZK 93423 and
diazepam was due to a decrease in the density of [35S]
TBPS recognition sites. On the other hand, the anxiogenic
beta-carbolines DMCM and
FG 7142 mimicked the effect of stress. Thus, at
a 10 microM concentration,
DMCM and
FG 7142 increased [35S]
TBPS binding by 22% and 26%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)