Drug effects on motor coordination

Summary

The rotarod test of motor coordination in mice was modified by increasing the rotation speed every 30 sec until the animals fell off. This procedure yielded a stable, proficient level of performance within four brief trials; the approximately normal distribution of performance times provided an equivalent measure of either improvement or impairment caused by drugs and permitted the use of parametric statistical tests. A total of 240 mice were assigned to 20 different groups of 12 each, administered oral doses of placebo or different drugs, prior to trial 4. The use of a ratio score (performance time in trial 4 divided by the same animal's time in trial 3) provided a measure of drug-induced changes, controlling for individual differences among animals in over-all level of performance. Two phenothiazines (chlorpromazine and perphenazine) impaired performance at low doses, with a progressively greater decrement at increasing doses (4, 8, 16 mg/kg); 2 barbiturates (pentobarbital and amobarbital) showed an all-or-none effect, with no significant decrement at the lower doses (20 and 40 mg/kg) but almost complete incapacitation at the highest dose of 80 mg/kg. Performance superior to the placebo condition was found with the 2 lower doses of pentobarbital and with 3 d-amphet-amine doses (4, 8, 16 mg/kg). An analysis of individual differences gave evidence that the animals which were inferior in prior performance were more susceptible to both improvement and impairment of performance under the influence of drugs.