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.

References

Galbraith, W.M. , and Hoar, R.M. (1984). Introduction: Species routinely used for toxicity testing. J. Am. Coll. Toxicol. 3: 323.

Beck, F . (1975). The ferret as a teratological model. In: New Approaches to the Evaluation of Abnormal Embryonic Development. D. Neubert and H.J. Merker (eds.). Acton, MA: Publishing Sciences Group Inc., pp. 8–20.

Beach, J.E. (1982). The ferret for non-rodent toxicity studies—A pathologist's view. Arch. Toxicol. [Suppl.] 5: 279–282.

Bleavins, M.R. , Aulerich, R.J. , and Ringer, R.K. (1980). Polychlorinated biphenyls (Aroclor 1016 and 1242): Effects on survival and reproduction in mink and ferrets. Arch. Environm. Contam. Toxicol. 9: 627–635.

Frederick, K.A. , and Babish, J.G. (1985). Compendium of recent literature on the ferret. Lab. Anim. Sci. 35: 298–318.

Hoar, R.M. (1984). Use of ferrets in toxicity testing. J. Am. Coll. Toxicol. 3: 325–330.

Ioannides, C. , Sweatman, B. , Richards, R. , and Parke, D.V. (1977). Drug metabolism in the ferret: Effects of age, sex and strain. Gen. Pharmacol. 8: 243–249.

Thornton, R.K. , Wright, P.A. , Sacra, P.J. , and Goodier, T.E.W. (1979). The ferret, Mustela putorius furo, as a new species in toxicology. Lab. Anim. 13: 119–124.

Lazar, J.W. , and Beckhorn, G.D. (1974). Social play or the development of social behavior in ferrets (Mustela putorius). Am. Zool. 14: 405–414.

10.

Poole, T.B. (1966). Aggressive play in polecats. Symp. Zool. Soc. Lond. 18: 23–44.

11.

Rabe, A. , Haddad, R. , and Dumas, R. (1985). Behavior and neurobehavioral teratology using the ferret. Lab. Anim. Sci. 35: 256–267.

12.

Hoar, R.M. (1981). Management and breeding of ferrets in a laboratory setting. Teratology 24: 11–12A.

13.

Moody, K.D. , Bowman, T.A. , and Lang, C.M. (1985). Laboratory management of the ferret for biomedical research. Lab. Anim. Sci. 35: 272–279.

14.

Winer, B.V. (1971). Statistical Principles in Experimental Design. New York: McGraw-Hill.

15.

Harris, L.W. , Lennox, W.J. , Talbot, B.G. , Anderson, D.R. , and Swanson, D.R. (1984). Toxicity of anticholinesterases: Interactions of pyridostigmine and physostigmine with soman. Drug Chem. Toxicol. 7: 507–526.

16.

Pradhan, S.N. , and Mhatre, R.M. (1970). Effects of anticholinesterases on behavior and cholinesterase activity in rats. Res. Commun. Chem. Path. Pharmacol. 5: 682–690.

17.

VAN Abeelen, J.H.F. , Smits, A.J.M. , and Raaijmakers, W.G.M. (1971). Central location of genotype-dependent cholinergic mechanism controlling exploratory behaviour in mice. Psychopharmacologia 19: 324–328.

18.

Meierl, G. , and Schmidt, W.J. (1982). No evidence for cholinergic mechanisms in the control of spontaneous predatory behavior in the ferret. Pharmacol. Biochem. Behav. 16: 677–681.

19.

Manthei, J. (1984). US Army Chemical Research and Development Center, Toxicology Division, Aberdeen Proving Ground, MD 21010. Personal communication.

20.

Gylys, J.A. (1986). Bristol-Myers Company, Syracuse, NY. Personal communication.

21.

Pope, D.J. , Gilbert, A.P. , Easter, D.J. , Chan, R.P. , Turner, J.C. , and Parke, D.V. (1981). The metabolism of bifluranol by rat, dog and ferret. J. Pharm. Pharmacol. 33: 302–308.