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Marshall-bred ferrets( n = 10) and Sprague-Dawley derived rats ( N = 12) were monitored in a photocell cage for 20 minutes following an IP injection of physostigmine salicylate or vehicle. Doses ranged from 0.0125 to 0.4 mg/kg for ferrets and 0.05 to 0.8 mg/kg for rats in equal logarithmic intervals. A repeated measures Latin-square design was used with a minimum of 72 hours between tests. Vertical activity (rearing), horizontal activity (ambulation), and movement time were recorded. Both ferrets and rats showed a reduction in rearing at doses of 0.1 mg/kg or greater. Ambulation was significantly reduced from vehicle control levels at doses of 0.05 mg/kg or greater for ferrets and 0.1 mg/kg or greater for rats. Ferrets exhibited a significant decrease in movement time at doses of 0.025 mg/kg or greater, whereas rats did not show this reduction until doses of 0.1 mg/kg or larger were administered. It thus appears that, using these behavioral measures, ferrets are more responsive to the effects of the cholinesterase inhibitor, physostigmine, than are rats.

Comparative Behavioral Toxicity of Physostigmine in Ferrets and Rats