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Changes in rat ambulatory activity and muscle tone after diazepam treatments (2.5, 5, 10, and 20 mg/kg orally) were compared under single and repeated (for 2, 4, 7, and 14 days) administration schedules. Ambulatory activity in the open field test was enhanced by a single dose of 2.5 mg/kg and reduced by 20 mg/kg. However, after all repeated treatment schedules, diazepam resulted in dose-dependent elevations of activity. Even with a treatment period of only 2 days, 20 mg/kg diazepam produced a marked increase in ambulation, which became more conspicuous with increases in the treatment periods. Acutely administered diazepam produced a dose-dependent reduction in muscle tone, but tolerance was noted to this effect during repeated administrations. Thus, time- and dose-dependent increases in ambulation during repeated treatments with diazepam can be partially explained by time-dependent tolerance development to its muscle relaxant effects. The enhancement in ambulation after short-term repetitive dosings of benzodiazepines can be used as a simple indicator for detecting their disinhibitory potentials.

Abstract-Caerulein(CLN

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