Potentiated modulation of pregnolone on GABA_A receptors in behaviorally stressed borderline-hypertensive rats

The modulatory effects of behavioral stress on [³H] flunitrazepam, an agonist for the central-type benzodiazepine receptor binding to the GABA_A-benzodiazepine receptor complex, in borderline hypertensive rats (BHR) were examined. In repeatedly immobilized (for 2 weeks, for 2 h/d) BHR, enhancement of [³H]flunitrazepam binding to the receptor was observed to be potentiated. The percent enhancement of [ ³H]flunitrazepam binding in BHR was higher than that in normotensive control Wistar-Kyoto rats. Pregnanolone, a neuroactive steroid that has been reported to be a putative endogenous modulator in the stress response, concentration dependently enhanced [³H]flunitrazepam binding to the receptor. Enhancement of [³H]flunitrazepam binding was observed to be potentiated by the same immobilized stress, and the EC₅₀ values of pregnanolone in BHR was significantly lower than those in controls and E _max values were higher. From the above results, it can be concluded that neural modulation to behavioral stress, especially in GABAergic neurotransmission, is exaggerated in BHR. We propose strain-specific differences of stress reactivity as an important pathogenetic factor in psychosomatic disorders including stress-induced hypertension. This is supported by reports showing exaggerated cardiovascular and symathoadrenal responses to stress in BHR.