Abstract

Though several studies have suggested that estradiol improves hippocampal-dependent spatial memory, the effects of other hormones in the hypothalamic–pituitary–gonadal axis on memory have largely been ignored. Estradiol and luteinizing hormone (LH) are generally inversely related and LH may significantly affect spatial memory. Ovariectomized (ovx) rats treated with Antide (a gonadotropin releasing hormone receptor antagonist) had low LH levels and showed enhanced spatial memory, comparable to treatment with estradiol. Antide-treated ovx females retained spatial memory longer than estradiol-treated ovx females. Deficits in spatial memory are a primary symptom of neurodegenerative disorders including Alzheimer's disease (AD). Treatment with Antide prevented spatial memory deficits in a neurotoxin-induced model typical of early AD. These data suggest that memory impairments seen in female rats after ovariectomy or women after menopause may be due to high LH levels and that a reduction in LH enhances memory. These results also implicate an LH lowering agent as a potential preventative therapy for AD.

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