Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Neuroendocrinology 2004;80:379–386 DOI: 10.1159/000084202 Effects of Estrogen on Muscarinic Acetylcholine Receptors in the Rat Hippocampus Camila C. Cardoso a Renato T.S. Pereira a Cristiane A. Koyama b Catarina S. Porto b Fernando M.F. Abdalla a a Laboratory of Pharmacology, Instituto Butantan, and b Section of Experimental Endocrinology, Department of Pharmacology, Universidade Federal de São Paulo-Escola Paulista de Medicina, São Paulo, Brazil of time after the loss of ovarian function may be effective at preventing specific effects of hormone deprivation on hippocampus. Copyright © 2004 S. Karger AG, Basel Introduction The cholinergic septo-hippocampal system has been associated with learning and memory, as evidenced by the severe loss of these functions in experimentally le- sioned animals and in Alzheimer’s disease patients [1]. Muscarinic acetylcholine receptors (mAChRs) modulate hippocampal function mainly by inhibiting synaptic ac- tivity and by increasing excitability of hippocampal neu- rons [2, 3]. Five mAChR subtypes are expressed in the mammalian brain (M 1 –M 5 ) and their coding genes have been cloned [see 4–7 for reviews]. mAChR subtypes are differently expressed in the rat hippocampus and often more than one subtype is present in one cell [5]. The effects of estrogen on mood, locomotor activity, pain sensitivity, vulnerability to epilepsy, attentional mechanisms and cognition have been reported in both animals and humans [see 8–10 for reviews]. An interac- tion of estrogen with cholinergic neurotransmission has also been shown in the central nervous system. Ovariec- tomy decreases the high affinity choline uptake as well as Key Words Acetylcholine receptors  Hippocampus  Ovariectomy  Gonadal steroids Abstract The aim of the present study was to investigate wheth- er different estrogen manipulations have effects on the expression of muscarinic acetylcholine receptors (mAChRs) in the adult female rat hippocampus. Hippo- campus was obtained from rats in proestrus (control), ovariectomized for 2, 10 and 15 days, ovariectomized for 15 days and treated with 17 -estradiol for 7 days, and treated with 17 -estradiol immediately after ovariecto- my for 21 days. Rats’ estrogen status was monitored by measuring estradiol plasma levels and uterus relative weight. [ 3 H]quinuclidinyl benzilate ([ 3 H]QNB) binding studies indicated that ovariectomy time-dependently in- creases the number of mAChRs in hippocampus when compared to those obtained from control rats. Estradiol treatments for 21 days avoid the effect of ovariectomy. However, the estradiol treatments for 7 days after 15 days of ovariectomy slightly change the number of mAChRs. In conclusion, these results showed that ovari- ectomy time-dependently increases mAChRs number in the rat hippocampus. In addition, these data suggest that treatment with estradiol initiated within a specific period Received: May 18, 2004 Accepted after revision: December 2, 2004 Published online: February 28, 2005 Fernando M.F. Abdalla Av Vital Brazil 1500 – São Paulo, SP 05503–900 (Brazil) Tel./Fax +55 11 3726 7222 E-Mail fabdalla@butantan.gov.br © 2004 S. Karger AG, Basel 0028–3835/04/0806–0379$21.00/0 Accessible online at: www.karger.com/nen