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      c- fos Expression in the Forebrain after Mating in the Female Rat Is Altered by Adrenalectomy

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          Abstract

          In rats of both sexes, mating stimulates neuronal activity in forebrain areas that are also activated by stress. Hypothalamic cells in the arcuate (ARC) and paraventricular (PVN) nuclei synthesize hormones or peptides whose levels are altered by adrenalectomy. In this experiment, we examined whether the mating-induced expression of c- fos in the forebrain is altered by adrenalectomy (Adx) in female rats. Ovariectomized females were adrenalectomized (Adx) or sham-operated (Sham), hormone-primed and mated 2 weeks after surgery. They received 15 intromissions (15I), 5 intromissions (5I) or 15 mounts without intromission (MO) from a male or were taken directly from their home cage (HC). Two hours after mating, rats were perfused with paraformaldehyde and their brains were collected and stained immunocytochemically for FOS protein. FOS-immunoreactive (FOS-IR) cells in the posterodorsal medial amygdala (MePD), bed nucleus of stria terminalis (BNST), ventromedial hypothalamus (VMH), medial preoptic area (mPOA), ARC and PVN were counted bilaterally. In Sham animals, intromissions produced significant increases in FOS above HC levels. In Adx animals, mating increased FOS activity in all areas. However, responses to 5I and 15I differed between Sham and Adx groups. In all areas, Shams showed either the highest FOS response following 15I or levels which were equivalent after 5I and 15I. In Adx animals, the greatest number of FOS-positive cells occurred after 5I, with the 15I group showing significant suppression of FOS below 5I levels in the VMH, mPOA, ARC and PVN. These results demonstrate that the adrenal modulates FOS responses to mating in the female rat and suggest that adrenal secretory products normally may decrease sensitivity to low levels of mating stimulation. These effects may be due to increased corticotropin-releasing hormone (CRH) or β-endorphin in the hypothalamus after adrenalectomy.

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          Most cited references19

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          Stressor categorization: acute physical and psychological stressors elicit distinctive recruitment patterns in the amygdala and in medullary noradrenergic cell groups.

          It has been hypothesized that the brain categorizes stressors and utilizes neural response pathways that vary in accordance with the assigned category. If this is true, stressors should elicit patterns of neuronal activation within the brain that are category-specific. Data from previous immediate-early gene expression mapping studies have hinted that this is the case, but interstudy differences in methodology render conclusions tenuous. In the present study, immunolabelling for the expression of c-fos was used as a marker of neuronal activity elicited in the rat brain by haemorrhage, immune challenge, noise, restraint and forced swim. All stressors elicited c-fos expression in 25-30% of hypothalamic paraventricular nucleus corticotrophin-releasing-factor cells, suggesting that these stimuli were of comparable strength, at least with regard to their ability to activate the hypothalamic-pituitary-adrenal axis. In the amygdala, haemorrhage and immune challenge both elicited c-fos expression in a large number of neurons in the central nucleus of the amygdala, whereas noise, restraint and forced swim primarily elicited recruitment of cells within the medial nucleus of the amygdala. In the medulla, all stressors recruited similar numbers of noradrenergic (A1 and A2) and adrenergic (C1 and C2) cells. However, haemorrhage and immune challenge elicited c-fos expression in subpopulations of A1 and A2 noradrenergic cells that were significantly more rostral than those recruited by noise, restraint or forced swim. The present data support the suggestion that the brain recognizes at least two major categories of stressor, which we have referred to as 'physical' and 'psychological'. Moreover, the present data suggest that the neural activation footprint that is left in the brain by stressors can be used to determine the category to which they have been assigned by the brain.
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            Sexual stimulation activates c-fos within estrogen-concentrating regions of the female rat forebrain.

            Regions of the brain that concentrate estrogen and progesterone are thought to regulate female sexual behavior by altering gene expression and neural sensitivity to afferent stimulation. We used immunocytochemistry and in situ hybridization to examine c-fos gene expression within estrogen-concentrating regions of the forebrain following various types of sexual stimulation with or without hormone treatment. Ovariectomized rats received injections of estradiol benzoate 48 h and progesterone 4 h before testing. Control rats that had been ovariectomized at least 5 months before testing did not receive hormone treatment. Rats were then either placed into bilevel testing chambers with sexually vigorous males, received manual stimulation of the flanks, received vaginocervical stimulation with a glass rod, or were left in their home cages. Copulation with intromission and ejaculation in hormone-treated rats, or stimulation of the vaginal cervix in both hormone-treated and control rats, produced a dramatic induction of c-fos mRNA and Fos-like immunoreactivity in estrogen-concentrating regions, such as the lateral septum, medial preoptic area, bed nucleus of the stria terminalis, paraventricular nucleus of the hypothalamus, ventromedial hypothalamus, lateral habenula, and medial amygdala, in addition to regions that do not readily concentrate estrogen, such as the neocortex, thalamus, and striatum. Mechanical stimulation of the flanks produced a smaller induction of Fos in these rats, whereas hormone treatment alone had no effect. These data demonstrate that afferent sensory stimulation, but not estrogen or progesterone, regulates c-fos gene expression within different estrogen-concentrating and non-concentrating regions of the female rat forebrain.
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              Paced copulation in rats: effects of intromission frequency and duration on luteal activation and estrus length.

              When estrous female rats regulate or pace (P) the timing of vaginal intromissions received from males during mating, the stimulation is more effective in inducing luteal function and abbreviating the period of receptivity than is nonpaced (NP) stimulation. The present studies examined whether the coital stimuli necessary for each of these functional consequences are similar. In Experiment 1, estrous females received either 5 or 10 intromissions from males in P or NP tests; control animals received mounts-without-intromission (MO). The duration of estrus was not affected by 5P, 5NP, or 10NP stimulation, but was significantly abbreviated in 10P animals. In contrast, activation of prolonged luteal function occurred in 70% of 5P females compared to only 10% of 5NP females; luteal activation was similar in 10P and 10NP females (74% for both groups combined). In Experiment 2, male copulatory behaviors were compared in tests with P and NP females. Males tested with P females exhibited significantly longer intromission durations (616 +/- 21 msec) than did males tested with NP females (527 +/- 30 msec). Other measures of male copulatory performance such as the number of intromissions to ejaculation and the ejaculation latency did not differ between groups. These studies demonstrate that luteal activation is more readily induced by paced coital stimulation than is abbreviation of estrus. In addition, they suggest that differences between P and NP females in the behavioral and neuroendocrine responses to coital stimulation may result from differences in intromission duration displayed by males under these test conditions.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2003
                June 2003
                13 June 2003
                : 77
                : 5
                : 305-313
                Affiliations
                Department of Biology, Boston University, Boston, Mass., USA
                Article
                70283 Neuroendocrinology 2003;77:305–313
                10.1159/000070283
                12806176
                d978fcc9-f14e-41b4-894c-a4f9058ddb5a
                © 2003 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 28 October 2002
                : 03 February 2003
                Page count
                Figures: 5, Tables: 1, References: 63, Pages: 9
                Categories
                Regulation of Reproductive Hormones

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Sexual behavior,<italic>fos</italic>,Adrenalectomy,Amygdala,Adrenal steroids,Arcuate nucleus,Paraventricular nucleus,Preoptic area

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