A comparison of the effects of RO15,1788 and chlordiazepoxide on hot-plate latencies, acoustic startle, and locomotor activity

Abstract

RO15,1788, (a selective benzodiazepine antagonist) and chlordiazepoxide (an anxiolytic 1,4-benzodiazepine) produced time-dependent and dose-dependent effects on various indices of sensory-motor function. RO15,1788 increased hot-plate latencies at doses (10-60 mg/kg) that had no effect on locomotor activity. Furthermore, the increased hot-plate latencies were observed 15, but not 30, 60, or 120 min after injection of 10 mg/kg RO15,1788. In contrast, chlordiazepoxide (2.5, 5.0, 10.0, 20.0 mg/kg) produced a dose-dependent increase in response times on the hot-plate, which appeared to be related to the depressant effects of this compound on motor activity. CDZ significantly decreased overall motor activity in a dose-related manner, with the two lower doses decreasing activity approximately 75% relative to controls. RO15,1788 (10 mg/kg) also decreased the magnitude of the acoustic startle response measured over 20 stimulus presentations. The startle response was significantly depressed during each of four 5-trial blocks. The magnitude of both the first and the largest response recorded was also decreased by this compound. Chlordiazepoxide (2.5 mg/kg) significantly decreased the magnitude of the startle response only during the first block of five stimulus presentations. These results are discussed in terms of the involvement of benzodiazepine-mediated processes in the modulation of sensory function and behavioral reactivity to biologically-relevant information.