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Biomedical subjects

W E Stumpf

Publications and source records attributed to W E Stumpf.

At least 73 records · Page 4Linked to original sources

High activity neurons in the reticular formation of the medulla oblongata: a high-resolution autoradiographic 2-deoxyglucose study.

Accumulation of radioactivity in the medulla oblongata of the rat was assessed with high resolution autoradiography after injection of [3H]2-deoxyglucose or [14C]2-deoxyglucose. The autoradiographic approach employed allowed analysis at the cellular level. A salient feature of autoradiograms was the presence of foci of very high silver grain density in the reticular formation. These heavily labeled foci were shown to be associated with neurons by combined Acridine Orange staining and autoradiography. The high activity neurons in the ventral lateral medulla were predominantly located in the caudal portion of the paragigantocellular reticular nucleus. In addition, a group of high activity neurons was present in the dorsal reticular formation. The potential involvement of the high activity neurons in cardiovascular and respiratory regulation is discussed. In dry-mount autoradiograms produced after injection of [3H]2-deoxyglucose, certain small cells, presumably glial cells, were observed throughout the brainstem to accumulate radioactivity to a greater extent than the surrounding tissue. High activity neurons and high activity glial cells were observed for 5 min and 45 min survival intervals after intravenous injection of [3H]2-deoxyglucose. The similar appearance of autoradiograms at 5 min and 45 min after injection of [3H]2-deoxyglucose indicates that the utility of a 5-min survival period deserves further evaluation for assessment of functional activity patterns in brain.

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Developmental changes in estrogen receptors in mouse cerebral cortex between birth and postweaning: studied by autoradiography with 11 beta-methoxy-16 alpha-[125I]iodoestradiol.

The presence of estrogen receptor cells in postnatal cerebral cortex and their topographical and numerical changes between birth and postweaning were examined. On postnatal days 0, 2, 8, 12, 18, and 25, six mice (three males and three females) were injected sc with 0.25 microgram/100 g BW 11 beta-methoxy-16 alpha-[125I]iodoestradiol [( 125I]MIE2). Two additional males on postnatal day 2 were each sc injected with 250 micrograms/100 g BW 17 beta-estradiol 1 h before radiolabeled ligand to establish the specificity of nuclear label. Two hours after the injection of [125I]MIE2 brains were frozen, and 4-microns sections were thaw-mounted and processed for autoradiography. Autoradiograms were exposed for 1-45 days, and cortical cells with nuclear uptake and retention of [125I]MIE2 were evaluated at the levels of the frontal pole, preoptic area, and central and posterior hypothalamus. At birth, cells with nuclear label were found predominantly in deep cortical layers. Between birth and postnatal day 2, the number of labeled cells increased in deep and intermediate laminae and first appeared in certain superficial regions. By day 8, labeled cells were concentrated in laminae II-VI of the cingulate/paracingulate and suprarhinal cortex. On day 12, labeling in laminae V and VI declined to a few cells, while a concentration of labeled cells remained in laminae II and III of the cingulate/paracingulate and suprarhinal regions. With subsequent development, an attenuation in labeling at all cortical levels was observed. By day 25, a small cluster of labeled cells remained in lamina II and III of the anterior cingulate, paracingulate, and suprarhinal regions, with additional labeled cells scattered throughout the remaining cortex. Competition with unlabeled 17 beta-estradiol reduced nuclear concentration of ligand in all cortical layers and demonstrated the specificity of [125I]MIE2 for the estrogen receptor. These results show the extensive presence of estrogen target cells in the early postnatal cortex and a profound change in topography and number of target cells during the postnatal period. These findings further suggest an important role for estrogen in the development of certain cortical neurons, possibly involving neuronal differentiation, cell positioning, and connectivity.

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Evidence for direct action of estradiol on growth hormone-releasing factor (GRF) in rat hypothalamus: localization of [3H]estradiol in GRF neurons.

Sex steroids have been shown to influence the secretion of GH. There appears to be no good evidence of the effect of estradiol on the anterior pituitary, while the central site of estradiol action on the regulation of GH secretion is not known. The present investigation was carried out to determine whether some of the GH-releasing factor (GRF) neurons and somatostatin (SRIF) neurons in the hypothalamus and GH cells in the pituitary contain estradiol receptors. Colocalization of [3H]estradiol and antibodies to GRF or SRIF in brain and antibodies to GH in pituitary was studied to show interrelationships between estrogen target cells and peptidergic cells. Eight female Sprague-Dawley rats were ovariectomized, each rat was treated with colchicine, and 24-48 h later the animals were given an iv injection of [2,4,6,7,16,17-3H]estradiol (SA, 166 Ci/mM) at a dose of 0.5 micrograms/100 g BW. One hour after the injection, the rats were perfused with 4% paraformaldehyde in 0.1 M phosphate buffer (pH 7.4). The hypothalami from the perfused rats and the pituitaries from unperfused rats were frozen in isopentane precooled in liquid nitrogen (-190 C) and processed for autoradiography. The brain autoradiograms were immunostained for GRF, SRIF, and tyrosine hydroxylase [TH; an enzyme for the synthesis of dopamine (DA)], and the pituitary autoradiograms were immunostained for GH by the avidin-biotin peroxidase method. The majority of GRF-containing neurons were found in the arcuate nucleus, with some scattered cells in the lateral region of the ventromedial nucleus and the basal lateral hypothalamus. In the central portion of the arcuate nucleus, 20-30% of GRF-containing neurons showed nuclear concentration of [3H]estradiol. In the anterior portion of the hypothalamus, 10-15% of immunoreactive GRF-containing neurons were labeled with [3H]estradiol. In the lateral basal hypothalamus and the lateral region to the ventromedial nucleus, a few GRF neurons showed nuclear concentration of radioactivity. In contrast, a few SRIF cells in hypothalamic periventricular nucleus showed nuclear labeling with [3H]estradiol. Dual immunostaining with GRF and TH antibodies revealed that the estradiol-labeled GRF neurons did not contain TH immunoreactivity. In addition, 80-90% of GH cells in the anterior pituitary showed nuclear concentration of [3H]estradiol. The present studies demonstrate for the first time that certain populations of GRF neurons are targets for estradiol and indicate that estradiol acts directly on certain hypothalamic GRF neurons. The results suggest that estradiol may have a role in the regulation of GH secretion by modulating GRF release and acting directly on the somatotrophs.

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Topography of oxytocinergic estradiol target neurons in the mouse hypothalamus.

Combined (3H) estradiol autoradiography and oxytocin immunocytochemistry were used in order to study co-localization of cytoplasmic oxytocin immunoreactivity and nuclear uptake of (3H) estradiol in the forebrain of adult ovariectomized mice. Labelling with (3H) estradiol was found in subpopulations of neurons that constitute between 10 to 40% of the oxytocinergic cells in the paraventricular nucleus, the supraoptic nucleus and the intersupraoptico-paraventricular islands. Oxytocinergic neurons in the septohypothalamic nucleus, the anterior commissural nucleus, the periventricular nucleus and the zona incerta only occasionally showed nuclear uptake of (3H) estradiol. The results indicate that oxytocinergic cell groups within the classical magnocellular nuclei have much higher numbers of estrogen receptors than the so called accessory oxytocin neurons. Oxytocinergic neuronal systems seem to constitute functionally heterogenous populations of cells, differently influenced by estradiol.

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Functional activity patterns in the forebrain of swimming rats: a 5 min 2-deoxyglucose study.

Effects of 5 min of swimming on functional activity patterns in the rat forebrain were examined by high resolution autoradiographic assessment of [14C]2-deoxyglucose ([14C]2-DG) uptake. In autoradiograms made from swimming rats, the isocortex displayed a columnar pattern in which columns of high optical density, oriented perpendicularly to the cortical surface, were separated by columns of low optical density of similar orientation. Increased [14C]2-DG uptake in swimming rats compared to resting rats was also apparent in the lateral septal nucleus, globus pallidus, and endopiriform nucleus. The results demonstrate that 2-DG can be used in short survival uptake experiments to gain insight into neuroanatomical patterns of functional activity.

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Atrial myoendocrine cells (cardiodilatin/atrial natriuretic polypeptide-containing myocardiocytes) are target cells for estradiol.

Atrial myoendocrine cells of rat were investigated regarding estradiol uptake. It was found that, in addition to their specific endocrine function of producing cardiac polypeptides of the cardiodilatin/atrial natriuretic peptide (CDD/ANP) family, these cells also specifically accumulate radiolabeled estradiol. This co-localization supports the view that steroid hormones play an important role in the regulation of the CDD/ANP gene.

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Changes in immunostaining for oxytocin in the forebrain of the female rat during late pregnancy, parturition and early lactation.

Serial brain sections of female rats at late pregnancy, parturition or early lactation were immunostained for oxytocin. Immunoreactive perikarya were visible in the magnocellular nuclei in all experimental animals as well as in ovariectomized, nulliparous controls. During late pregnancy and at parturition additional immunostaining appeared in groups of perivascular neurons in the preoptic region, the lateral subcommissural nucleus, the perifornical region and scattered throughout the ventral portion of the hypothalamus. Immunostaining of almost all of these perivascular neurons disappeared by day two postpartum, while another population of oxytocin neurons, without association with blood vessels, appeared in these brain regions after parturition. Immunostaining of processes from oxytocinergic neurons in the periventricular nucleus increased markedly near parturition. Many of these processes projected toward the third ventricle. Oxytocinergic neuronal systems that are activated in late pregnancy and early postpartum may contribute to several physiological changes associated with parturition and lactation including the onset of maternal behavior.

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Light, vitamin D and psychiatry. Role of 1,25 dihydroxyvitamin D3 (soltriol) in etiology and therapy of seasonal affective disorder and other mental processes.

This is a review and a prospectus of effects of vitamin D on the brain. Effects of sunlight and equivalent artificial light on physiological and behavioral processes are probably mediated, in large part, through the skin-vitamin D-endocrine system. Experimental evidence from our laboratory reveals sites of action and concomitant direct effects of 1,25(OH)2 vitamin D3 (soltriol) on brain, spinal cord, pituitary and other endocrine tissues. This appears relevant for the activation and modulation of mental and endocrine processes, particularly related to seasonal and daily biorhythms. Effects of sunlight and corresponding artificial light are likely to be mediated through direct actions of soltriol on brain and endocrine tissues that are independent of its effect on calcium levels. Those direct actions are receptor mediated and appear to be dose related as they depend on intensity of light and length of exposure, considering light (photons) as a drug. A role for soltriol, the steroid hormone of sunlight, in the etiology and helio- or phototherapy of affective disorders with cyclic seasonal onset (seasonal affective disorder) is discussed and the significance of research in the new frontier of vitamin D and brain relationships is noted.

Calcitriol↗

Dexamethasone and corticosterone receptor sites. Differential topographic distribution in rat hippocampus revealed by high resolution autoradiography.

High resolution light microscopic autoradiography was used, together with regional surveys and combined acridine orange staining, to define in rat hippocampus cellular and subcellular sites of concentration and retention of 3H dexamethasone and to compare the topographic pattern of labeling with that of 3H corticosterone. Nuclear uptake of 3H dexamethasone in the hippocampus is demonstrated for the first time in vivo. With 3H dexamethasone, strongest nuclear radioactive labeling was observed in certain glial cells throughout the hippocampus, followed by strong nuclear labeling in most neurons in area CA1 and in the adjacent dorsolateral subiculum and weak nuclear labeling in granule cells of the dentate gyrus. Neurons in areas CA2, CA3, CA4, and in the dorsomedial subiculum and indusium griseum showed little or no nuclear labeling after 3H dexamethasone. With 3H corticosterone, strongest nuclear labeling was observed in neurons in area CA2 and in the dorsomedial subiculum and indusium griseum, followed by area CA1, then CA3 and CA4; the dentate gyrus contained scattered strongly labeled cells among cells with intermediate nuclear labeling. At the subcellular level, evidence for both nuclear and cytoplasmic accumulation of label was found. The results indicate that dexamethasone and corticosterone have both nuclear and cytoplasmic binding sites and that particular patterns of target cell distribution exist, characteristic for each agent. This suggests a differential regulation of cellular functions for the two compounds. Corticosterone nuclear binding appears to be more extensive and encompasses regions with dexamethasone binding. Whether in certain of these common regions corticosterone binds to the same receptor as dexamethasone, which seems possible, or to different receptors, remains to be clarified.

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Autoradiographic localization of [3H]hydroxytamoxifen to uterine oestrogen- and antioestrogen-binding sites.

Immature rats were injected subcutaneously with 0.36 micrograms of [3H]hydroxytamoxifen ([3H]TAM(OH)) or 0.24 microgram of [3H]oestradiol in oil, and 4 h later uteri were processed for thaw-mount autoradiography. The specificity of [3H]TAM(OH) localization was determined by injecting a 200-fold excess of unlabelled TAM(OH) or a 20-, 200- or 2000-fold excess of oestradiol 1 h before injection of [3H]TAM(OH). After injection of [3H]TAM(OH) or [3H]oestradiol, autoradiograms showed concentration of radioactivity in nuclei of stromal, epithelial and myometrial cells, but this labelling varied among the cell types depending upon which compound was injected. After [3H]TAM(OH) injection, the decreasing order of labelling intensity was stroma, myometrium, epithelium; after [3H]oestradiol injection the decreasing order was stroma, epithelium, myometrium. Injection of TAM(OH) before [3H]TAM(OH) eliminated nuclear labelling in all the uterine cell types. Injection of oestradiol before [3H]TAM(OH) decreased nuclear labelling and resulted in the concentration of label in the cytoplasm of luminal epithelium which was not present when [3H]TAM(OH) was injected alone. Cytoplasmic labelling increased initially as the oestradiol competition dose increased, but the increase in labelling did not continue with increasing concentrations of oestradiol. The results indicate that antioestrogen and oestrogen localize to nuclei of the same uterine cell types, but that cellular uptake differs among the tissue compartments. The results also suggest that a high concentration of antioestrogen-binding sites exist in the cytoplasm of the uterine luminal epithelium.

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Vitamin D (soltriol), light, and reproduction.

Evidence from autoradiographic studies with 1,25(OH)2-vitamin D3 (vitamin D, soltriol) labeled with tritium and from the literature indicates that the steroid hormone soltriol regulates and modulates reproductive processes in the female, as it does in the male. Nuclear receptors for soltriol have been discovered in the uterus, oviduct, ovary, mammary gland, placenta, and fetal membranes, as well as in the pituitary and hypothalamus. Soltriol is recognized as a transducer and hormonal messenger of sunlight, acting as a somatotropic activator and modulator of vital processes for the seasonal and estival adaptation of growth, development, and procreation. Its influence on calcium equilibrium is just one of its many functions to serve this goal. This article reviews experimental, clinical, and epidemiologic evidence that suggests the involvement of soltriol in the control of reproductive processes, noting its importance for the onset of puberty, fertility, pregnancy, lactation, and probably sexual behavior. Cooperative actions between soltriol and other steroid hormones, especially estradiol, are pointed out.

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Differential nuclear binding of [3H]testosterone and its metabolites to androgen and estrogen receptors in brain, pituitary, heart, kidney and accessory sex glands of the mouse: an autoradiographic study.

Nuclear binding of [3H]testosterone ([3H]T) was studied by autoradiography in brain and peripheral tissues of normal male mice and androgen receptor (AR) deficient Tfm (testicular feminized) mice at various time points after injection. All tissues examined contain AR and estrogen receptors (ER). Nuclear binding (accumulation of radioactive hormone) was characterized by competition with excess of dihydrotestosterone (DHT) or estradiol (E2) and by inhibition of aromatization (AI). 2 h after injection of [3H]T, nuclear binding is found in certain regions of the forebrain of male and Tfm mice, but only in area postrema of hindbrain and in accessory sex glands of males. In pituitary, heart and kidney no nuclear binding is observed. In brain, except for area postrema, binding is inhibited by competition with E2 or by AI. DHT has no effect. This indicates predominant binding to ER. In the area postrema and in accessory sex glands binding is inhibited by DHT but not by E2, indicating binding only to AR. After [3H]T together with E2 or AI, additional nuclear binding is found in certain regions of the brain and in pituitary, unlabeled after [3H]T alone and after [3H]T with DHT. It suggests binding to AR which becomes detectable by an increased amount of androgen available for AR. Up to 1 h after [3H]T in the brain, binding is detectable at more sites than after 2 h. This additional binding is not suppressible by E2, indicating binding to AR. Since this additional binding is found only within the first hour after injection, a difference in binding to AR between brain and accessory sex glands after [3H]T is suggested.

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No evidence for aromatization of [3H]testosterone in oestrogen receptor containing cells of the epididymis.

Oestrogen receptors are found in the principal cells of the caput and in apical and clear cells of the epididymis of the mouse. The distribution pattern of oestrogen receptors is different from that of androgen receptors and suggests a physiological role for oestrogens in the epididymis. We examined by competition experiments and thaw-mount autoradiography to see whether aromatization of [3H]testosterone is the source of oestrogens in the epididymis. After injection of [3H]testosterone we found the same labeling pattern as after non-aromatizable [3H]dihydrotestosterone. In particular, apical and clear cells showed a low or no nuclear concentration of radioactivity as with [3H]dihydrotestosterone. Competition with oestradiol had no effect on the binding pattern of [3H]testosterone in the epididymis in contrast to its effects in the brain of the same animals. Competition with dihydrotestosterone abolished labeling in contrast to the brain, where no effect was observed. Thus no aromatization of [3H]testosterone to oestrogens but conversion to dihydrotestosterone seems to occur in the epididymis.

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Topographical assessment of accumulated radioactivity from [14C]2-deoxyglucose and [6(-14C)]glucose in rat forebrain at different survival periods.

The uptake and retention of radioactivity was measured in discrete areas of rat brain at different times after i.v. injection of [14C]2-deoxyglucose or [6(-14)C]glucose, in unrestrained rats. In most brain regions, the accumulation of radioactivity from the two compounds was similar when a 30-min survival period for [6(-14)C]glucose was compared to a 45-min survival period for [14C]2-deoxyglucose. However, at those times, autoradiographic images of the hippocampus and piriform cortex appeared distinctly different for [14C]2-deoxyglucose and [6(-14)C]glucose. Relatively more radioactivity accumulated from [14C]2-deoxyglucose, compared to [14C]glucose, in the stratum lacunosum-moleculare of the hippocampus and in layer 4 of the isocortex. In contrast, relatively more radioactivity accumulated from [6(-14)C]glucose, compared to [14C]2-deoxyglucose, in the molecular and granule cell layers of the dentate gyrus, the CA1 pyramidal cell layer of the hippocampus, and in layer 2 of the piriform cortex. When rats were killed 5 min after injection of [6(-14)C]glucose, the relative neuroanatomical distribution of radioactivity was similar to the 30-min survival period, except in layer 4 of the isocortex, where relatively more radioactivity was present at the early time. When rats were killed 5 min after injection of [14C]2-deoxyglucose, in 20 of 24 brain regions examined, the absolute and relative amounts of accumulated radioactivity were similar when compared to that of the 45-min survival period. In contrast, the absolute and relative amounts of radioactivity were significantly greater for the 5-min compared to the 45-min survival period, in the CA1 pyramidal cell field, dentate gyrus, and layer 2 of the piriform cortex. For those regions, the appearance of autoradiograms prepared from rats killed 5 min after administration of [14C]2-deoxyglucose is remarkably similar to the appearance of autoradiograms prepared from rats killed 5 or 30 min after injection of [6(-14)C]glucose. Possible mechanisms are discussed to explain the observed differences in the accumulation of radioactivity in discrete brain regions after injection of [6(-14)C]glucose and [14C]2-deoxyglucose at the different survival times examined.

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Metabolic mapping of functional activity in rat brain and pituitary after water deprivation.

Glucose utilization in rat brain and pituitary was measured in control and water-deprived rats by autoradiographic assessment of the metabolic trapping of radioactivity from [1-14C]glucose. Two days of water deprivation resulted in significant increases in hematocrit, plasma osmolality and vasopressin levels, indicating a functional activation of magnocellular vasopressin neurons. The uptake and retention of radioactivity from [1-14C]glucose in the dehydrated rats, compared to controls, was 103% greater in the magnocellular portion of the paraventricular nucleus and 74% greater in the supraoptic nucleus. Water deprivation also resulted in significant increases in glucose utilization (30-40%) in the lateral and anterior hypothalamic areas, somatosensory cortex and cingulate cortex. No change in glucose utilization after 2 days of water deprivation was apparent in the parvocellular paraventricular nucleus, periventricular nucleus of the hypothalamus, corpus callosum, organum vasculosum of the lamina terminalis (OVLT) or the subfornical organ (SFO). In the pituitary, glucose utilization was increased in the neural lobe but was unchanged in the anterior and intermediate lobes after water deprivation. Under the conditions of the present study, no increase in metabolic activity was apparent in 2 brain regions thought to be possible sources of osmoreception, the OVLT and SFO. These results do not support, but do not exclude, functional involvement of the OVLT and SFO in regulating the activity of magnocellular neurons of the paraventricular nucleus and supraoptic nucleus during chronic water deprivation.

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Distribution of soltriol [1,25(OH)2-vitamin D3] binding sites in male sex organs of the mouse: an autoradiographic study.

After injection of [3H]-1,25(OH)2-vitamin D3 (soltriol), nuclear labeling is found in Sertoli cells of testes, being highest at the stage of spermiosis, in epithelium of efferent ductules and caput epididymidis and in connective tissue cells of epididymis, in lamina propria and muscular sheath of deferent duct, and in epithelium and muscular sheath of dorsal and ventral prostate of the mouse. This labeling pattern is characteristic for [3H]-soltriol and differs from that for [3H]-dihydrotestosterone and [3H]-estradiol, although with overlap. The nuclear labeling with [3H]-soltriol suggests an action of the hormone on certain processes during spermatogenesis, on sperm maturation, on epididymal fluid resorption, and on secretion and transport of spermatozoa.

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Progestin receptors in brain and pituitary of 20-day-old fetal mice: an autoradiographic study using [125I]progestin.

The distribution of progestin target sites in the brain and pituitary of estrogen-primed 20-day-old fetal mice was investigated by thaw-mount autoradiography. Three pregnant mice were each implanted sc with a Silastic tube containing estrogen on day 17 and ovariectomized on day 19 of gestation. Twenty-four hours after ovariectomy 10 fetuses (5 males and 5 females) were collected and each injected sc with 0.33 microgram/100 g BW [125I]progestin (SA, 2200 Ci/mM). For competition, two additional fetuses were injected with 20 micrograms R5020 1 h before (Z)-17 beta-hydroxy-17 alpha-(2[125I]iodovinyl)4-estren-3-one [( 125I]Progestin) to demonstrate that nuclear uptake and retention of radioactivity were specific for progestin. Two hours after injection of [125I]Progestin all fetuses were mounted, frozen, and sectioned in a cryostat. After 1-37 days of exposure, sections were developed and scanned for labeled cells. Cells with nuclear concentration were found in the male and female preoptic area, within certain nuclear groups in the basal hypothalamus, in the central gray of the midbrain, and in the pituitary. No labeling was detected in the cortex or amygdala. The results indicate that cells in certain regions of the brain and pituitary express progestin receptors at the end of gestation and suggest that progesterone is important for the normal development of these cells.

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Neuroanatomically selective down-regulation of beta adrenergic receptors by chronic imipramine treatment: relationships to the topography of [3H]imipramine and [3H] desipramine binding sites.

The down-regulation of beta adrenergic receptors by chronic imipramine treatment was investigated with high resolution autoradiography of [125I]pindolol binding to brain sections. Neuroanatomically selective down-regulation of [125I]pindolol binding was found after chronic imipramine treatment. Subdivisions of the amygdala and hippocampus and discrete cortical regions were differentially affected. In the hippocampus, reduction of [125I]pindolol binding was observed in imipramine-treated rats in the CA-1 stratum radiatum and dentate molecular layer, but not in the CA-3 stratum radiatum. In the amygdala, the basolateral nucleus exhibited reduced [125I]pindolol binding after imipramine treatment but the central and medial nuclei were not affected. Chronic imipramine treatment was also associated with reduced [125I]pindolol binding in layer 1 of the cingulate cortex and layer 3 of the piriform cortex. In contrast, no effect on [125I]pindolol binding was apparent in the ventrolateral thalamic nucleus, caudate-putamen, lateral hypothalamus or layers 2 and 3 of the somatosensory cortex. In order to determine if regional variation in binding sites for imipramine, or its pharmacologically active metabolite desipramine, was responsible for the observed neuroanatomically selective reduction in [125I]pindolol binding, the binding of [3H]imipramine and [3H]desipramine was investigated. In some brain regions that exhibited high densities of [3H]imipramine and [3H]desipramine binding sites, [125I]pindolol binding was reduced after chronic treatment with imipramine. However, other regions that contained high densities of binding sites for antidepressant drugs did not show a reduction in [125I]pindolol binding after chronic imipramine treatment. Thus, regional binding of [3H]imipramine or [3H]desipramine cannot fully explain the neuroanatomical specificity of imipramine-induced beta adrenergic receptor down-regulation.(ABSTRACT TRUNCATED AT 250 WORDS)

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