Abstract

The present study describes an objective, cost- and time-efficient procedure for characterizing the ataxic effects of psychoactive drugs. Male Sprague–Dawley rats were administered an intraperitoneal injection of either saline or one of three doses (1, 5 or 10 mg/kg) of phencyclidine (PCP) 15 min prior to being placed into an empty standard operant conditioning chamber (all manipulanda were removed). The floor of the test apparatus consisted of parallel rows of metal rods spaced approximately 1.5 cm apart. During a 5-min test, a single observer counted the frequency with which each animal's paws (front or back) slipped between the rows of bars that constituted the cage floor. The data demonstrated that while saline animals exhibited no instability in their ambulation, PCP-treated animals demonstrated a highly reliable dose-dependent increase in the number of “paw slips” in a single trial. Since animals are known to develop tolerance to the ataxic response to PCP, the validity of the test as a measure of drug-induced ataxia was examined in a separate group of animals treated with the middle (5 mg/kg) dose every other day over the course of a 9-day period (i.e., resulting in five injection trials). In this experiment, each subsequent test produced a reliable reduction in the magnitude of the ataxic response, and by the fifth drug challenge, the PCP animals were performing at near-control levels. These results suggest that the “paw slip test” can serve as a simple, reliable, objective and valid measure of drug-induced ataxia. The relevance of the ataxia data for interpreting the locomotor response of animals treated with PCP is also discussed.

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