title: Sex differences in dizocilpine (MK-801) neurotoxicity in rats.
abstract: The sex differences in the clinical signs and the distribution of astrocytic glial fibrillary acidic protein (GFAP) induced by an N-methyl-d-aspartate antagonist, dizocilpine (MK-801), were examined. A single intraperitoneal injection of MK-801 (5 mg/kg body weight) caused a prolonged recumbency (35-40 h), leading to a severe loss of body weight in female rats, in contrast to a light effect in males, independent of age. Early salivation or lacrimation was also severe in females and delayed bloody lacrimation was observed in females only. The pretreatment with 17β-estradiol (0.1 or 1.0 mg/kg body weight) made early signs worse in both sexes, but a remarkable mortality (20-40%) was observed in females only. The treatment with MK-801 greatly enhanced GFAP expression in retrospenial cortex of both sexes with a higher enhancement in females. The MK-801-induced expression of GFAP was further increased by the pretreatment with 17β-estradiol (1 mg/kg body weight) in females. Overall, the expression of GFAP in the retrospenial cortex of rats treated with MK-801 appeared to be higher in females than males, somewhat in parallel with more severe clinical signs in females. The results indicate the higher sensitivity of female rats to MK-801 neurotixicity, and the possible involvement of 17β-estradiol in the sex differences of the sensitivity.
authors.affiliation: Biomedical Assessment Laboratory (1-3-4), Agency for Defense Development, Yuseong P.O. Box 35-1, Taejon 305-600, South Korea.
authors.forename: G H
authors.initials: GH
authors.lastname: Hur
authors.forename: W C
authors.initials: WC
authors.lastname: Son
authors.forename: S
authors.initials: S
authors.lastname: Shin
authors.forename: J K
authors.initials: JK
authors.lastname: Kang
authors.forename: Y B
authors.initials: YB
authors.lastname: Kim