Sensitivity to the effects of sedative-hypnotics on motor performance: influence of task difficulty and chronic...

The present investigation examined sensitivity to the effects of various sedative-hypnotics on motor performance in rats treated chronically with phenobarbital. Eight rats were trained to walk on a rotorod treadmill at low (8 r.p.m.) and high (24 r.p.m.) rotational speeds. Prior to the chronic regimen, phenobarbital, pentobarbital, amobarbital, diazepam and clonazepam produced dose-dependent impairments in motor performance at both speeds. During chronic treatment with phenobarbital (100 mg/kg/day), tolerance was conferred to the effects of all the drugs examined, as evidenced by rightward shifts in their dose-effect curves. For all drugs, the magnitude of this tolerance was generally consistent across the two speeds. Following a 6-week washout period, during which no drugs were administered, dose-effect curves for each drug shifted back toward their original (i.e. pre-chronic) positions. Under all conditions, the doses required for each drug to impair motor performance at the low speed were higher than those required to impair motor performance at the high speed. These data suggest that sensitivity to the motor-impairing effects of sedative-hypnotics is influenced by the difficulty of the behavioral task, but that task difficulty does not modulate the maximal extent to which tolerance and cross-tolerance are expressed.