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 reinforce ment. Each 360-degrees rotation counted as a single response. Three fo od pellets were delivered for each reinforcement. The wheels, which pr ovided transverse rods to be gripped by the rats, were specifically de signed to reflect motor deficits produced by neurotoxicants. Each anim al received two replicates of three different doses of methanol (50% i n water): 1.0, 2.0, and 3.0 g/kg by gavage. The sequence for each anim al was determined by a counterbalanced design. Gavage was followed by admitting the animal to the running wheel compartment 10 min later. Ru nning wheel sessions lasted for 1 hour daily and were conducted 6 days /week. Statistical analyses showed insignificant differences between w ater 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) i ndicated a displacement of the distribution toward longer intervals (d ecreased velocities) with increasing dose. The absence of a correspond ing rise in the incidence of long pauses suggested that impaired coord ination, reduced endurance, or their combination, rather than nonspeci fic variables, accounted for these results.