Comparative Behavioral Toxicity of Physostigmine in Ferrets and Rats

Abstract

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.