Alterations in Locomotor Activity Induced by Radioprotective Doses of 16,16-Dimethyl Prostaglandin E2
16, 16-Dimethyl prostaglandin E2 (DiPGE2) is an effective radioprotectant when administered before irradiation. A notable side effect of this compound is sedation. In separate experiments, we investigated the dose-response determinations of the time course of locomotor activity and 30-day survival after 10 Gy gamma irradiation (LD100). Adult male CD2F1 mice were injected subcutaneously with vehicle or DiPGE2 in doses ranging from 0.01 to 40 μg/mouse. A dose of 0.01 μg did not result in alterations in locomotor behavior or enhance survival. Doses greater than 1 μg produced ataxia and enhanced radiation survival in a dose-dependent fashion. Full recovery of locomotor activity did not occur until 6 and 30 hr after injection for the 10 μg and 40-μg groups, respectively. Radioprotection was observed when DiPGE2 was administered preirradiation but not postirradiation. Doses of 1 and 10 μg were maximally effective as a radioprotectant if injected 5 min prior to irradiation (80%–90% survival). A dose of 40 μg resulted in 100% survival when injected 5–30 min before irradiation. Therefore, increasing doses of DiPGE2 resulted in enhanced effectiveness as a radioprotectant. However, the doses that were the most radioprotective were also the most debilitating to the animal.
KeywordsLocomotor Activity Locomotor Behavior Vehicle Control Group Mental Alertness Radioprotective Activity
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- 10.Fleiss, J. L. “Statistical Methods for Rates and Proportions.” John Wiley, New York, 1981, pp. 138–143.Google Scholar
- 12.Landauer, M. R., Davis, H. D., Dominitz, J. D., and Weiss, J. F. Comparative behavioral toxicity of four sulfhydryl radioprotective compounds in mice. WR-2721, cysteamine, diethyldithiocarbamate, and N-acetylcysteamine. Parmac. Ther., in press.Google Scholar
- 13.Landauer, M. R., Davis, H. D., Dominitz, J. D., and Weiss, J. F. Long-term effects of radioprotector WR-2721 on locomotor activity and body weight of mice following exposure to ionizing radiation. Toxicology, in press.Google Scholar
- 14.Bito, L. Z., Davson, H., and Hollingsworth, J. R. Facilitated transport of prostaglandins across the blood-cerebrospinal fluid and blood-brain barriers. J. Physiol. 253: 273–285, 1976.Google Scholar
- 16.Hayaishi, O. Prostaglandin D2: A neuromodulator. In: “Advances in Prostaglandin, Thromboxane, and Leukotriene Research,” Vol. 12. B. Samuelsson, R. Paoletti, and P. Ramwell, eds. Raven Press, New York, 1983, pp. 333–337.Google Scholar