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Human & Experimental Toxicology
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Malaoxon-Induced Brain Phosphoinositide Turnover and Changes in Brain Calcium Levels by Female Gender in Pregnant and Non-Pregnant Convulsing and Non-Convulsing Rats

M.-R. Hirvonen

Division of Environmental Health, National Public Health Institute, P.O. Box 95; SF-70701 Kuopio

K.M. Savolainen

Division of Environmental Health, National Public Health Institute, P.O. Box 95; SF-70701 Kuopio, Department of Pharmacology and Toxicology, University of Kuopio; P.O. Box 1627, SF-70211 Kuopio, Finland

Alterations in malaoxon-(MO)-induced brain regional phosphoinositide (PI) turnover and in brain calcium levels were studied in female non-pregnant and pregnant rats, and in their offspring. The adult rats were followed for 1 or 4 h after MO for tonic-clonic convulsions. A dose of 8.2 mg kg-1 of MO caused similar convulsions in 74% of the pregnant rats as we have reported in young male rats with a dose of 39.2 mg kg-1,1 However, convulsions did not occur in non-pregnant female rats. Inositol and inositol monophosphate levels were similar in all control rats. MO decreased brain inositol both in pregnant and non-pregnant female rats, and in the cerebellum of the offspring. In contrast to the findings in male rats, MO only randomly increased brain inositol-1-phosphate in female rats, or in their offspring. However, cerebral inositol-4-phosphate levels were similarly increased both in the non-pregnant and the pregnant rats irrespectively of convulsions. MO did not elevate cerebral Ca2+ in female rats or their offspring, in contrast to the male rats. 1 The present results suggest that female rats are more sensitive than male rats to MO-induced PI signalling, and during pregnancy, also to MO-induced overt convulsions, but not to changes in cerebral Ca2+.

Human & Experimental Toxicology, Vol. 12, No. 6, 469-477 (1993)
DOI: 10.1177/096032719301200604
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