Estrogens influence behavioral responses in a kainic acid model of neurotoxicity.
The behavioral and neuroprotective effects of 17beta-estradiol (E2), on ovariectomized rats treated with a subconvulsive dose (7 mg/kg bw, ip) of kainic acid (KA), were examined. Estradiol was administered either acutely (150 mug/rat, ip) along with KA, 14 days post-ovariectomy, or chronically (sc capsules providing proestrus estrogen levels in serum) starting at ovariectomy. Exploratory behavior, as deduced by sniffing in the open field test, was reduced in KA-treated rats. Both hormonal schemes partially restored sniffing behavior in KA-lesioned subjects. Moreover, acute and chronic E2 administration in KA-treated rats resulted in increased vertical and horizontal activity of these animals in the open field test. Memory for object recognition was reduced following KA and was not restored by hormonal treatments. Acute, but not chronic, E2 coadministration with KA significantly impaired spatial performance in the water maze task, while KA alone had no effect. Both acute and chronic estradiol administration rescued hilar and CA1 neurons from KA-induced cell death. Chronic, but not acute, E2 increased neurofilament immunoreactivity in the mossy fibers of the dentate gyrus neurons, similarly to KA. Our results show that although estradiol administration in KA-treated rats has beneficial effects on cell survival, it has diverse effects on exploratory behavior, object, and spatial memory. Estradiol effects on KA-lesioned animals depended on the duration and timing of exposure to the hormone, implying different mechanisms of hormone actions.
Papalexi
Eugenia
E
Laboratory of Histology and Embryology, Athens University Medical School, Mikras Asias 75, Goudi 11527, Athens, Greece.
Antoniou
Katerina
K
Kitraki
Efthimia
E
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D004958:Estradiol / Q000378:metabolism* / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D007608:Kainic Acid; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D023421:Models, Animal; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000503:physiopathology*; D009498:Neurotoxins; D010052:Ovariectomy; D051381:Rats; D017208:Rats, Wistar; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
D018696:Neuroprotective Agents; D009498:Neurotoxins; D004958:Estradiol; D007608:Kainic Acid