Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To elucidate the mechanism of psychostimulant-induced reverse tolerance [A. Kifune, S. Tadokoro, Modification of stereotype producing and ambulation-increasing effects following repeated administration of methamphetamine in rats, Jpn. J. Psychopharmacol. 11 (1991) 207-214 [11]; N.J. Leith, R. Kuczenski, Chronic amphetamine: tolerance and reverse tolerance reflect different behavioral actions of the dog, Pharmacol. Biochem. Behav. 15 (1981) 399-405 [13]; S. Tadokoro, H. Kuribara, Reverse tolerance to the ambulation-increasing effect of methamphetamine in mice as an animal model of amphetamine-psychosis, Psychopharmacol, Bull. 22 (1986) 757-762 [18]; S. Tadokoro, H. Kuribara, Modification of the behavioral effects of drugs after repeated administration: special reference to the reverse tolerance, Folia Pharmacologica Japonica 95 (1990) 229-238 [19]], the effects of lithium on ambulatory activity [P. Cappeliez, E. Moore, Effects of lithium on an amphetamine animal model of bipolar disorder, Prog. Neuro-Psychopharmacol. Biol. Psychiatry 14 (1990) 347-358 [1]; M. Hirabayashi, M.K. Alam, Enhancing effect of methamphetamine on ambulatory activity produced by repeated administration on mice, Pharmacol. Biochem. Behav. 15 (1981) 925-932 [7]; M. Hirabayashi, S. Okada, S. Tadokoro, Comparison of sensitization to ambulation-increasing effects of cocaine and methamphetamine after repeated administration in mice, J. Pharm. Pharmacol. 43 (1991) 827-830 [8]; T. Miyauchi, K. Kikuchi, S. Satoh, Further studies on the potentiating effect of lithium chloride on methamphetamine-induced stereotypy in mice, Jpn. J. Pharmacol. 31 (1981) 61-68 [14]; H. Ozawa, T. Nozu, H. Aihara, F. Akiyama, M. Sasajima, Pharmacokinetics and general pharmacological actions of lithium salts administered singly or repeatedly, Folia Pharmacologica Japonica 72 (1976) 433-443 [15].] and cerebral c-Fos expression [S. Ceccatelli, M.J. Villar, M. Goldstein, T. Hokfelt, Expression of c-Fos immunoreactivity in transmitter-characterized neurons after stress, Proc. Natl. Acad. Sci. USA 86 (1989) 9569-9573 [2]; L. Giovannelli, P.J. Shiromani, G.F. Jirikoski, F.E. Bloom, Expression of c-fos protein by immunohistochemically identified oxytocin neurons in the rat hypothalamus upon osmotic stimulation, Brain Research 588 (1992) 41-48 [4]; B.T. Hope, H.E. Nye, M.B. Kelz, D.W. Self, M.J. Iadarola, Y. Nakabeppu, R.S. Duman, E.J. Nestler, Induction of a long-lasting AP-1 complex composed of altered Fos-like proteins in brain by chronic cocaine and other chronic treatments, Neuron 13 (1994) 1235-1244 [10]; T. Miyauchi, K. Kikuchi, S. Satoh, Further studies on the potentiating effect of lithium chloride on methamphetamine-induced stereotypy in mice, Jpn. J. Pharmacol. 31 (1981) 61-68 [14]; F.R. Sharp, S.M. Sager, K. Hicks, D. Lowenstein, K. Hisanaga, c-fos mRNA, Fos, and Fos-related antigen induction by hypertonic saline and stress, J. Neurosci. 11 (1991) 2321-2331 [16].] were investigated in mice injected with methamphetamine (2 mg/kg, s.c., one to five times). The ambulatory activity enhanced by either acute or chronic methamphetamine injection was delayed or diminished by lithium chloride (LiCl) pretreatment [R.G. Fessler, R.D. Sturgeon, S.F. London, H.Y. Meltzer, Effects of lithium on behaviour induced by phencyclidine and amphetamine in rats. Psychopharmacology 78 (1982) 373-376 [3].]. How the Li-sensitive c-Fos expression in the dorsolateral geniculate nucleus and striatum is related to methamphetamine-induced behavioral excitation is unclear. This protocol, in combination with c-Fos expression of mouse cerebral regions, may provide a useful tool for quantitation of ambulatory activity during c-Fos expression.
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PMID:Quantitative analysis of the effects of lithium on the reverse tolerance and the c-Fos expression induced by methamphetamine in mice. 1023 48

In sheep, birth leads to the induction of maternal behaviour through brain oxytocin release. Associated with these events is an upregulation of oxytocin, opioid and corticotrophin-releasing hormone (CRH) gene expression, as well as that of the immediate early gene c-fos in the paraventricular nucleus (PVN) of the hypothalamus. We investigated the role of c-fos dimerizing with c-jun in controlling the induction of maternal behaviour, altered peptide gene expression, and oxytocin and amino acid release in this region at birth. Fluorescence-labelled antisense oligodeoxyribonucleotides (ODNs) against c-fos/c-jun were infused bilaterally in the PVN, via microdialysis probes with 100 kDa cut-off membranes, and were incorporated into 50-60% of the cells. Compared with the control (scrambled) sequences, they significantly reduced basal concentration of glutamate (to 31.7% of baseline after 10 h) and prevented birth-induced release of aspartate. In addition, antisense treatment reduced the birth-induced increase in oxytocin concentration in the PVN, but not in blood. Although all the animals were fully maternal, the antisense treatment did reduce the peak expression of two components of maternal behaviour: low-pitched bleats; and lamb sniffing. Finally, in situ hybridization histochemistry revealed that the antisense treatment significantly reduced the birth-induced upregulation of c-fos, oxytocin, CRH and preproenkephalin mRNA expression in the PVN, whilst not affecting that of arginine vasopressin. These results suggest that c-fos/c-jun transcription factors play a role in the birth-induced upregulation of oxytocin, CRH and preproenkephalin gene expression, as well as on glutamate and oxytocin release in the sheep PVN.
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PMID:C-fos and c-jun in the paraventricular nucleus play a role in regulating peptide gene expression, oxytocin and glutamate release, and maternal behaviour. 1038 9

The amygdala plays a pivotal role in the generation of appropriate responses to emotional stimuli. In the case of emotional stressors, these responses include activation of the hypothalamic-pituitary-adrenal (HPA) axis. This effect is generally held to depend upon the central nucleus of the amygdala, but recent evidence suggests a role for the medial nucleus. In the present study, c-fos expression, amygdala lesion and retrograde tracing experiments were performed on adult rats in order to re-evaluate the role of the central as opposed to the medial amygdala in generating neuroendocrine responses to an emotional stressor. Brief restraint (15 min) was used as a representative emotional stressor and was found to elicit c-fos expression much more strongly in the medial than central nucleus of the amygdala; relatively few Fos-positive cells were seen in other amygdala nuclei. Subsequent experiments showed that ibotenic acid lesions of the medial amygdala, but not the central amygdala, greatly reduced restraint-induced activation of cells of the medial paraventricular nucleus, the site of the tuberoinfundibular corticotropin-releasing factor cells that constitute the apex of the HPA axis. Medial amygdala lesions also reduced the activation of supraoptic and paraventricular nucleus oxytocinergic neurosecretory cells that commonly accompanies stress-induced HPA axis activation in rodents. To assess whether the role of the medial amygdala in the control of neuroendocrine cell responses to emotional stress might involve a direct projection to such cells, retrograde tracing of amygdala projections to the paraventricular nucleus was performed in combination with Fos immunolabelling. This showed that although some medial amygdala cells activated by exposure to an emotional stressor project directly to the paraventricular nucleus, the number is very small. These findings provide the first direct evidence that it is the medial rather than the central amygdala that is critical to hypothalamic neuroendocrine cell responses during an emotional response, and also provide the first evidence that the amygdala governs oxytocin as well as HPA axis responses to an emotional stressor.
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PMID:Neuroendocrine responses to an emotional stressor: evidence for involvement of the medial but not the central amygdala. 1038 20

We performed c-fos expression experiments in conscious rats to quantify the threshold and extent of activation of hypothalamic neuroendocrine cells in response to non-hypotensive and hypotensive hemorrhages allowing us to assess whether their pattern of recruitment corresponded to known oxytocin, vasopressin and ACTH release patterns. Also, because previous studies have implicated ventrolateral medulla catecholamine cells in the generation of certain hypothalamic neuroendocrine cell responses, we examined the response of ventrolateral medulla catecholamine cells to non-hypotensive and hypotensive hemorrhages and directly tested their role in regulating neuroendocrine cell responses to hypotensive hemorrhage. Animals were subjected to hemorrhages of 0, 4, 8, 12 or 16 ml/kg BW, the latter two levels being hypotensive. We found that only supraoptic nucleus vasopressin cells were significantly activated by the smallest non-hypotensive hemorrhage (4 ml/kg), which corresponds to reports that only vasopressin is released into the plasma after a small hemorrhage. Hypotensive hemorrhages resulted in significant recruitment of paraventricular and supraoptic oxytocin and vasopressin cells and parvocellular cells of the medial division of the paraventricular nucleus. Vasopressin cells were recruited in much greater numbers than oxytocin cells, which is in agreement with previous findings that there is a greater release of vasopressin than oxytocin into the plasma after hypotensive hemorrhage. In addition, medial parvocellular cells of the paraventricular nucleus, most likely to be tuberoinfundibular-projecting corticotropin-releasing factor cells, were activated by hypotensive hemorrhage only when arterial pressure dropped below 60 mmHg which also corresponds well with the plasma release response of ACTH. Ventrolateral medulla catecholamine cells were only recruited by hypotensive hemorrhages. While caution must be exercised in interpreting an absence of response, this certainly suggests that catecholamine cells are unlikely to have a role in the activation of supraoptic neurosecretory cells in response to non-hypotensive hemorrhages. Unilateral lesions of the ventrolateral medulla catecholamine cell column, corresponding primarily to the location of A1 noradrenergic cells, significantly reduced the hypotensive hemorrhage-induced activation of hypothalamic vasopressin, oxytocin and medial parvocellular paraventricular nucleus cells. This suggests that A1 noradrenergic cells contribute to the activation of these neuroendocrine cell populations, including oxytocin cells, which is an unexpected finding. More significantly, however, because the reduction in responsiveness after A1 lesions was similar for all cell categories, it seems likely that other factors must determine the differential recruitment of hypothalamic neuroendocrine cells in response to a hypotensive hemorrhage.
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PMID:Differential recruitment of hypothalamic neuroendocrine and ventrolateral medulla catecholamine cells by non-hypotensive and hypotensive hemorrhages. 1040 92

Distinct brain peptidergic circuits govern peripheral energy homeostasis and related behavior. Here we report that mitochondrial uncoupling protein 2 (UCP2) is expressed discretely in neurons involved in homeostatic regulation. UCP2 protein was associated with the mitochondria of neurons, predominantly in axons and axon terminals. UCP2-producing neurons were found to be the targets of peripheral hormones, including leptin and gonadal steroids, and the presence of UCP2 protein in axonal processes predicted increased local brain mitochondrial uncoupling activity and heat production. In the hypothalamus, perikarya producing corticotropin-releasing factor, vasopressin, oxytocin, and neuropeptide Y also expressed UCP2. Furthermore, axon terminals containing UCP2 innervated diverse hypothalamic neuronal populations. These cells included those producing orexin, melanin-concentrating hormone, and luteinizing hormone-releasing hormone. When c-fos-expressing cells were analyzed in the basal brain after either fasting or cold exposure, it was found that all activated neurons received a robust UCP2 input on their perikarya and proximal dendrites. Thus, our data suggest the novel concept that heat produced by axonal UCP2 modulates neurotransmission in homeostatic centers, thereby coordinating the activity of those brain circuits that regulate daily energy balance and related autonomic and endocrine processes.
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PMID:Brain uncoupling protein 2: uncoupled neuronal mitochondria predict thermal synapses in homeostatic centers. 1057 39

In the present study we examined the role of the central nucleus of the amygdala in hypothalamic-pituitary-adrenal axis responses to an immune challenge in the form of systemic administration of the proinflammatory cytokine interleukin-1beta (1 microg/kg). We found that bilateral ibotenic acid lesions of the central amygdala substantially reduced adrenocorticotropin hormone release and hypothalamic corticotropin-releasing factor and oxytocin cell c-fos expression responses to interleukin-1,8 suggesting a facilitatory role for this structure in the generation of hypothalamic-pituitary-adrenal axis responses to an immune challenge. Since only a small number of central amygdala cells project directly to the paraventricular nucleus, we then examined the effect of central amygdala lesions on the activity of other brain nuclei that might act as relay sites in the control of the hypothalamic-pituitary-adrenal axis function. We found that bilateral central amygdala lesions significantly reduced interleukin-1beta-induced c-fos expression in cells of the ventromedial and ventrolateral subdivisions of the bed nucleus of the stria terminalis and brainstem catecholamine cell groups of the nucleus tractus solitarius (A2 noradrenergic cells) and ventrolateral medulla (A1 noradrenergic and C1 adrenergic cells). These findings, in conjunction with previous evidence of bed nucleus of the stria terminalis and catecholamine cell group involvement in hypothalamic-pituitary-adrenal axis regulation, suggest that ventromedial and ventrolateral bed nucleus of the stria terminalis cells and medullary catecholamine cells might mediate the influence of the central amygdala on hypothalamic-pituitary-adrenal axis responses to an immune challenge. Thus these data establish that the central amygdala influences hypothalamic-pituitary-adrenal axis responses to a systemic immune challenge but indicate that it primarily acts by modulating the activity of other control mechanisms.
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PMID:The central amygdala modulates hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta administration. 1061 7

We measured stimulation of c-fos and oxytocin gene expression during excitation of oxytocin cells induced by systemic or local morphine withdrawal. Female rats were made morphine-dependent by intracerebroventricular morphine infusion over 5 d. Morphine withdrawal, induced by systemic injection of the opioid antagonist naloxone (5 mg/kg) in conscious or anesthetized rats, increased the density of c-fos messenger RNA and of oxytocin heterogeneous nuclear RNA in supraoptic nucleus cells compared with those of nonwithdrawn rats; c-fos messenger RNA was also increased in the magnocellular and parvocellular paraventricular nuclei of withdrawn rats. Morphine withdrawal increased the number of Fos-immunoreactive cells in the supraoptic and magnocellular paraventricular nuclei of conscious or pentobarbitone-anesthetized rats. Morphine withdrawal also increased Fos-immunoreactive cell numbers in the parvocellular paraventricular nucleus of conscious but not anesthetized rats. Central administration of the alpha(1)-adrenoreceptor antagonist benoxathian (5 microg/min) did not prevent morphine withdrawal-induced increases in the numbers of Fos-immunoreactive neurons in the supraoptic or magnocellular paraventricular nucleus. Unilateral microdialysis administration of naloxone (10(-5) M) into the supraoptic nucleus of anesthetized morphine-dependent rats increased Fos-immunoreactive cell numbers compared with the contralateral nucleus. Finally, we investigated whether dependence could be induced by chronic unilateral infusion of morphine into a supraoptic nucleus; systemic naloxone (5 mg/kg) increased Fos-immunoreactive cell numbers in the morphine-infused nucleus compared with the contralateral nucleus. Thus, morphine withdrawal excitation increases c-fos and oxytocin gene expression in supraoptic nucleus neurons. This occurs independently from excitation of their ascending noradrenergic inputs, and both dependence and withdrawal can be induced within the supraoptic nucleus.
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PMID:Local morphine withdrawal increases c-fos gene, Fos protein, and oxytocin gene expression in hypothalamic magnocellular neurosecretory cells. 1064 31

We have recently shown that intracerebroventricular (i.c.v.) administration of the hypothalamic neuropeptide cocaine-amphetamine-regulated transcript (CART) inhibits food intake and induces the expression of c-fos in several nuclei involved in the regulation of food intake. A high number of CART-induced c-Fos-positive nuclei in the paraventricular nucleus of the hypothalamus prompted us to examine the effect of i.c.v. recombinant CART-(42-89) on activation of CRH-, oxytocin-, and vasopressin-synthesizing neuroendocrine cells in the paraventricular nucleus (PVN). In addition, plasma levels of glucose were examined after central administration of CART-(42-89). Seventy-six male Wistar rats were fitted with i.c.v. cannulas and singly housed under 12-h light, 12-h dark conditions. One week postsurgery the animals were injected i.c.v. in the morning with 0.5 microg recombinant CART-(42-89) or saline. Trunk blood was collected by decapitation at 0 (baseline), 10, 20, 40, 60, 120, or 240 min. CART caused a strong increase in circulating corticosterone that was significantly different from saline at 20, 40, 60, and 120 min postinjection (P<0.05). Furthermore, CART caused a transient rise in plasma oxytocin levels (P<0.05 at 10 and 20 min postinjection), whereas plasma vasopressin levels were unaffected by i.c.v. CART. Animals injected i.c.v. with CART showed a rise in blood glucose levels 10 min postinjection (P<0.05). To examine whether the stimulatory effect of i.c.v. CART on corticosterone and oxytocin secretion is caused by activation of paraventricular nucleus/supraoptic nucleus (PVN/SON) neuroendocrine neurons, we used c-Fos as a marker of neuronal activity. Animals injected with CART showed a strong increase in c-Fos-immunoreactive nuclei in the PVN. Double immunohistochemistry revealed that a high (89+/-0.4%) number of CRH-immunoreactive neurons in the PVN contained c-Fos after CART i.c.v.. c-Fos expression was also observed in oxytocinergic cells (in both magnocellular and parvicellular PVN neurons as well as in the supraoptic nuclei) 120 min after CART administration, whereas none of the vasopressinergic neurons contained c-Fos. Triple immunofluorescence microscopy revealed that CART-immunoreactive fibers closely apposed c-Fos-positive CRH neurons, suggestive of a direct action of CART on PVN CRH neurons. In summary, i.c.v. CART activates central CRH neurons as well as both magnocellular (presumably neurohypophysial) and parvicellular (presumably descending) oxytocinergic neurons of the PVN. The effect of CART on CRH neurons most likely leads to corticosterone secretion from the adrenal gland, which may contribute to the inhibitory effects of CART on feeding behavior.
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PMID:Central administration of cocaine-amphetamine-regulated transcript activates hypothalamic neuroendocrine neurons in the rat. 1065 Sep 62

The glucostatic theory supports the role of central and peripheral substrate "sensors" in monitoring cellular glucose metabolism. Induction of hyperphagia and hyperglycemia by intracerebroventricular (i.c.v.) delivery of drugs inhibiting glucose uptake or oxidation suggests that glucose "sensors" are accessible from the cerebroventricular system. Although glucopenia elevates neurohypophyseal vasopressin (VP) and oxytocin (OXY) secretion and induces c-fos expression by hypothalamic paraventricular (PVN) and supraoptic (SON) neurons, the origin of glucoprivic regulatory signals impinging upon these cell populations is unclear. The following study evaluated immunolabeling of hypothalamic VP and OXY neurons for the nuclear transcription factor, Fos, following systemic vs. i.c.v. delivery of the glucose antimetabolite, 2-deoxy-D-glucose (2DG). Intraperitoneal drug treatment resulted in Fos expression by a high proportion of AVP- and OXY-ir neurons in the PVN and SON, whereas i.c.v. antimetabolite administration resulted in immunostaining of a smaller proportion of AVP neurons and a lack of colabeling of OXY neurons in both sites. These results suggest that decreased glucose metabolism within the periventricular CNS is a stimulus for central mechanisms that activate the Fos stimulus-transcription cascade in a discrete subpopulation of VP neurons in the PVN and SON. Alternatively, the absence of demonstrable Fos expression by OXY neurons in the same structures suggests that the functional status of these cells is regulated by glucoprivic stimuli of peripheral and/or nonperiventricular central origin.
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PMID:Intraventricular 2-deoxy-D-glucose induces Fos expression by hypothalamic vasopressin, but not oxytocin neurons. 1071 20

Adrenomedullin, a potent hypotensive peptide, was originally isolated from human phaeochromocytoma. Adrenomedullin immunoreactivity and gene expression are found not only in peripheral organs but also in the central nervous system. Adrenomedullin labelled cells were localised in the hypothalamus, including in the paraventricular and supraoptic nuclei, in rats. Abundant adrenomedullin-immunoreactive fibres and varicosities were found in the hypothalamo-neurohypophysial tract and the internal zone of the median eminence in colchicine-treated and hypophysectomized rats, whereas in control rats few adrenomedullin-labelled fibres were observed. We examined the effects of intracerebroventricular administration of adrenomedullin on neurosecretory cells in the paraventricular and supraoptic nuclei of rats, using immunohistochemistry for Fos protein and in situ hybridisation histochemistry for c-fos mRNA. Intracerebroventricular administration of adrenomedullin caused a marked induction of Fos-like immunoreactivity in the paraventricular nucleus and the dorsal part of the supraoptic nucleus. In the paraventricular and supraoptic nuclei, nuclear Fos-like immunoreactivity was predominantly in oxytocin-immunoreactive cells rather than vasopressin-immunoreactive cells. The induction of c-fos mRNA in the paraventricular and supraoptic nuclei was increased in a dose-related manner 30 min after intracerebroventricular administration of adrenomedullin. This induction was reduced by pre-treatment with the adrenomedullin receptor antagonist, human adrenomedullin-(22-52)-NH2. Intracerebroventricular administration of adrenomedullin also caused a marked increase in the plasma concentration of oxytocin. Extracellular recordings from magnocellular neurosecretory cells in the paraventricular nucleus revealed that putative oxytocin-secreting cells were activated by intracerebroventricular administration of adrenomedullin. These results suggest that central adrenomedullin preferentially stimulates the secretion of oxytocin by activating hypothalamic oxytocin-secreting cells and may have an important role in salt appetite and body fluid homeostasis in rats.
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PMID:A physiological role for adrenomedullin in rats; a potent hypotensive peptide in the hypothalamo-neurohypophysial system. 1079 19


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