Effects of raloxifene and estradiol on hippocampal acetylcholine release and spatial learning in the rat.
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.
Gibbs
Robert B
RB
Department of Pharmaceutical Sciences, University of Pittsburgh School of Pharmacy, 1004 Salk Hall, Pittsburgh, PA 15261, USA. gibbsr@pitt.edu
Gabor
Rachel
R
Cox
Teresa
T
Johnson
David A
DA
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects* / Q000502:physiology; D017551:Microdialysis; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D014599:Uterus / Q000187:drug effects
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D000109:Acetylcholine