Neurobehavioral toxicity of methanol reflected by operant running

Eleven Long-Evans male rats were trained to respond for food delivery by running in wheels under a Fixed Ratio = FR 20 schedule of reinforcement. Each 360° rotation counted as a single response. Three food pellets were delivered for each reinforcement. The wheels, which provided transverse rods to be gripped by the rats, were specifically designed to reflect motor deficits produced by neurotoxicants. Each animal received two replicates of three different doses of methanol (50% in water): 1.0, 2.0, and 3.0 g/kg by gavage. The sequence for each animal was determined by a counterbalanced design. Gavage was followed by admitting the animal to the running wheel compartment 10 min later. Running wheel sessions lasted for 1 hour daily and were conducted 6 days/week. Statistical analyses showed insignificant differences between water and no-treatment control days, indicating no effect of the gavage procedure. However, a dose-effect relationship between methanol dose and responses per session proved statistically significant and linear (p < 0.0001) down to a dose equivalent to 10% of the LD50. In addition, detailed analyses of intervals between successive rotations (IRTs) indicated a displacement of the distribution toward longer intervals (decreased velocities) with increasing dose. The absence of a corresponding rise in the incidence of long pauses suggested that impaired coordination, reduced endurance, or their combination, rather than nonspecific variables, accounted for these results.