Effects of raloxifene and estradiol on hippocampal acetylcholine release and spatial learning in the rat

doi:10.1016/S0306-4530(03)00118-5

Psychoneuroendocrinology

Volume 29, Issue 6, July 2004, Pages 741-748

https://doi.org/10.1016/S0306-4530(03)00118-5 Get rights and content

Abstract

The effects of raloxifene on acquisition of a delayed matching to position (DMP) T-maze task and on hippocampal acetylcholine release were evaluated and compared with estradiol, to determine whether raloxifene has estrogenic effects on cognitive performance and hippocampal cholinergic activity. Ovariectomized rats received continuous treatment with raloxifene (one of two doses), estradiol, or vehicle for 30 days, followed by behavioral training, and then in vivo microdialysis assessment of basal and potassium-stimulated acetylcholine release. The data show that estradiol significantly enhanced DMP acquisition, whereas raloxifene did not. In contrast, both estradiol and the higher dose of raloxifene significantly increased potassium-stimulated acetylcholine release in the hippocampus. These data suggest that, despite increasing evidence for estrogenic effects of raloxifene in brain, raloxifene does not mimic the effects of estrogen on cognitive performance as assessed by acquisition of a simple spatial memory task in ovariectomized rats.

Section snippets

Methods

Forty-five young adult (275–300 g) Sprague-Dawley rats were purchased from Hilltop Laboratories. All procedures involving animals were conducted in compliance with state and federal laws, standards of the United States Department of Health and Human Services, and guidelines established by the University of Pittsburgh Institutional Animal Care and Use Committee. All animals were ovariectomized in-house, and then housed individually with food and water freely available. All animals were housed

Uterine size

As expected, the uterus in E-treated animals was much larger than in controls (73.8±12.1 mg/cm for E-treated animals vs. 14.3±0.6 mg/cm for controls). In contrast, treatment with raloxifene did not appear to affect uterine size or weight (17.7±1.1 mg/cm for HR-treated animals, and 17.0±0.7 mg/cm for LR-treated animals). ANOVA revealed a significant effect of treatment on uterine mass/cm (F[3,41]=26.7, p<0.00001). Post-hoc analysis confirmed that uterine tissue from E-treated animals weighed

Discussion

Consistent with previous reports (Gibbs, 1999, Gibbs, 2002), the data show that chronic estradiol replacement significantly enhanced acquisition of the DMP task, as well as potassium-stimulated acetylcholine release in the hippocampus of ovariectomized rats. In addition, the data show that, like estrogen, chronic high dose raloxifene treatment significantly enhanced potassium-stimulated acetylcholine release in the hippocampus; however, in contrast to estrogen, raloxifene did not significantly

Acknowledgments

We wish to acknowledge Rajesh Nagle for providing excellent technical assistance. This work was supported by a grant from Eli Lilly, Inc.

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Effects of raloxifene and estradiol on hippocampal acetylcholine release and spatial learning in the rat

Abstract

Section snippets

Methods

Uterine size

Discussion

Acknowledgments

Front Neuroendocrinol.

Psychoneuroendocrinology

Psychoneuroendocrinology

Neuropsychopharmacology

Pharmacol. Biochem. Behav.

Brain Res.

Brain Res.

Horm. Behav.

Neurobiol. Aging

Horm. Behav.

Horm. Behav.

Brain Res.

Brain Res.

Brain Res.

Psychoneuroendocrinology

Neurobiol. Learn. Mem.

Psychiatry Res. Neuroimaging

Brain Res.

Brain Res.

Lancet

Brain Res.

Prog. Neurobiol.

Brain Res.

Estrogen augments glucose transporter and IGF1 expression in primate cerebral cortex

FASEB J.