Effect of β-carboline-3-carboxoylate-t-butyl ester on ventilatory control

β-carboline-3-carboxylate-t-butyl ester (βCCT) is the most selective antagonist for the α 1 β 2 γ 2 benzodiazepine (BZ) receptor subtype which blocks anticonvulsant and antipunishment (anxiolytic) but not sedative and myorelaxant effects of diazepam. We sought to determine whether the α 1 β 2 γ 2 BZ receptor subtype modulates ventilation and whether βCCT antagonizes respiratory depressant effects of BZ's. Room air (RA) ventilation and the ventilatory response to 6% & 12% CO 2 were non-invasively assessed by barometric plethysmography in 30gm mice, n = 11. Plethysmograph signal amplitude (AMP), respiratory rate (RR) and minute ventilatory effort (MVE = AMP∗RR), were measured. Runs were performed pre-drug & after IP injection of saline, vehicle for βCCT, βCCT (60 mg kg ), midazolam (10 mg kg ), and midazolam followed by βCCT. Compared with pre-drug values, midazolam depressed MVE during RA and CO 2 stimulation (% of pre-drug value: RA :57.7 ± 17.4%, 6% CO 2 : 53.73 ± 14.3%, 12%CO 2 : 69.1 ± 26.1%, p < .0001, ANOVA). Subsequent βCCT partially reversed this depression during RA conditions (72.8 ± 25.7% of pre-drug value, p < .03 compared with midazolam) and 6% CO 2 stimulation (67.1 ± 10.7% of pre-drug value, p < .006 compared with midazolam) but not with 12% CO 2. Thus, the α 1 β 2 γ 2 BZ receptor subtype modulates ventilation and βCCT partially antagonizes respiratory depressant effects of BZ's.