Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aripiprazole is a newer atypical antipsychotic agent used for effective treatment of schizophrenia. It significantly reduces unwanted side effects of older typical antipsychotics by targeting, with high affinity, dopamine D2/D3 and serotonin 5-HT1A/5-HT-2A receptors. Its documented mechanism of action makes it an unlikely agent to cause syndrome of inappropriate antidiuretic hormone secretion (SIADH). We present the first reported case of SIADH caused by aripiprazole in a patient with history of schizophrenia without other precipitating factors to explain hyponatremia or SIADH.
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PMID:Aripiprazole-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH). 1685 73

Schizophrenia, many believe, reflects an enhanced vulnerability to psychological stress. Controlled exposure to stressors, however, has produced inconclusive results, particularly with regards to neurohormones. Some of the variability may be attributable to the nature and psychological significance of the stimulus and failure to control physiologic confounds. In addition, it is possible that the heterogeneity of schizophrenia is an important factor. In a carefully designed study and in a controlled setting, we measured the neuroendocrine response of eight polydipsic hyponatremic (PHS), seven polydipsic normonatremic (PNS), and nine nonpolydipsic normonatremic (NNS) (ie normal water balance) schizophrenic in-patients as well as 12 healthy controls (HC) to two different stressors: one of which appears to influence neuroendocrine secretion through its psychological (cold pressor) and the other (upright posture) through its systemic actions. Subjects in the three psychiatric groups were stabilized and acclimated to the research setting, and all received saline to normalize plasma osmolality. Following the cold pressor, plasma adrenocorticotropin and cortisol levels showed a more prolonged rise in PHS patients relative to PNS patients. NNS patients, in contrast, exhibited blunted responses relative to both of the polydipsic groups and the HC. Peak vasopressin responses were also greater in PHS and blunted in NNS patients. Responses to the postural stimulus were similar across patient groups. These findings provide a mechanism for life threatening water intoxication in schizophrenia; help to reconcile conflicting findings of stress responsiveness in schizophrenia; and potentially identify a discrete patient subset with enhanced vulnerability to psychological stress.
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PMID:Neuroendocrine responses to a cold pressor stimulus in polydipsic hyponatremic and in matched schizophrenic patients. 1716 13

A 27-year-old man with schizophrenia took an overdose of a psychotic agent. He became unconscious and had severe hypotension. Although he was diagnosed as having distributive shock caused by drug overdose and treated by hydration and catecholamine, the shock status was lasting. The use of vasopressin changed the situation dramatically. After the injection of vasopressin at maximum dose, 0.1 U/min, the dose of vasopressin could be tapered. He recovered from shock and was discharged on the third day without sequelae. There are an increasing number of reports that indicate that vasopressin is effective for distributive shock, especially catecholamine-resistant septic shock. It seems that the appropriate dose of vasopressin is under 0.04U/min considering the deterioration of cardiac function although the maximum dose of vasopressin was O.1U/min in this case. For that reason, monitoring by pulmonary artery catheter is recommended. The side effects of vasopressin should be discussed for appropriate use.
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PMID:[Case of catecholamine-resistant shock caused by drug overdose]. 1731 3

Neuropeptides are heterogeneously distributed throughout the digestive, circulatory, and nervous systems and serve as neurotransmitters, neuromodulators, and hormones. Neuropeptides are phylogenetically conserved and have been demonstrated to regulate numerous behaviors. They have been hypothesized to be pathologically involved in several psychiatric disorders, including schizophrenia. On the basis of preclinical data, numerous studies have sought to examine the role of neuropeptide systems in schizophrenia. This chapter reviews the clinical data, linking alterations in neuropeptide systems to the etiology, pathophysiology, and treatment of schizophrenia. Data for the following neuropeptide systems are included: arginine-vasopressin, cholecystokinin (CCK), corticotropin-releasing factor (CRF), interleukins, neuregulin 1 (NRG1), neurotensin (NT), neuropeptide Y (NPY), opioids, secretin, somatostatin, tachykinins, thyrotropin-releasing hormone (TRH), and vasoactive intestinal peptide (VIP). Data from cerebrospinal fluid (CSF), postmortem and genetic studies, as well as clinical trials are described. Despite the inherent difficulties associated with human studies (including small sample size, variable duration of illness, medication status, the presence of comorbid psychiatric disorders, and diagnostic heterogeneity), several findings are noteworthy. Postmortem studies support disease-related alterations in several neuropeptide systems in the frontal and temporal cortices. The strongest genetic evidence supporting a role for neuropeptides in schizophrenia are those studies linking polymorphisms in NRG1 and the CCKA receptor with schizophrenia. Finally, the only compounds that act directly on neuropeptide systems that have demonstrated therapeutic efficacy in schizophrenia are neurokinin receptor antagonists. Clearly, additional investigation into the role of neuropeptide systems in the etiology, pathophysiology, and treatment of schizophrenia is warranted.
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PMID:Involvement of neuropeptide systems in schizophrenia: human studies. 1734 66

Neurodevelopmental changes induced by environmental stress exposure play a significant but poorly defined role in the etiology of schizophrenia. Exposure of pregnant female rats to a series of unpredictable stresses during the final week of pregnancy generates behavioral deficits and molecular changes in the offspring similar to those observed in schizophrenic individuals. We used this rat prenatal stress preparation to investigate social withdrawal behaviors that may have relevance to the negative symptoms of schizophrenia. The cumulative time adult male offspring of stress-exposed pregnant female rats actively interacted with a weight-matched, same-sex peer was decreased approximately 76% relative to non-stress exposed control rats. Prenatal stress exposure also diminished the quality of the social interaction behavior indicative of reduced social drive. Analysis of the oxytocinergic system in the prenatally stressed male rats revealed significantly less oxytocin mRNA in the paraventricular nucleus and increased oxytocin receptor binding in the central amygdala. Moreover, oxytocin, but not vasopressin, administration into the central amygdala reversed the social incompetence of the prenatally stressed rats without increasing behavior in non-stressed control animals. In addition, cross-fostering pups from prenatally stressed mothers to non-stressed mothers failed to improve the social deficit of the prenatally stressed male offspring. Two behavioral assays designed to measure anxiety did not differentiate the prenatally stressed rats from non-stressed controls. These data indicate that prenatal stress may be an etiologically appropriate animal model for some aspects of schizophrenic social withdrawal. Furthermore, unpredictable prenatal stress exposure selectively degrades social interaction behaviors without increasing anxiety measures.
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PMID:Prenatal stress generates deficits in rat social behavior: Reversal by oxytocin. 1754 Mar 47

We previously reported that vasopressin deficient Brattleboro (BRAT) rats exhibit deficits in prepulse inhibition (PPI) of the startle reflex that are consistent with PPI deficits exhibited by patients with schizophrenia and other neuropsychiatric disorders. Preliminary evidence indicates that this may be the basis of a predictive model for antipsychotic drug efficacy. Here we report the effects of acute and chronic administration of established and putative antipsychotics on these PPI deficits. BRAT rats, compared to their derivative strain, Long Evans rats, exhibited significantly decreased PPI and startle habituation consistent with patients with schizophrenia and other neuropsychiatric disorders. The second generation antipsychotics, risperidone and clozapine as well as a neurotensin agonist (PD149163) increased BRAT rat PPI, whereas saline, the typical antipsychotic, haloperidol, and a vasopressin analog (1-desamino-D-arginine vasopressin) did not. Similar to their effects in humans, chronic administration of antipsychotic drugs produced stronger effects than acute administration. These results further support the BRAT rat as a model of sensorimotor gating deficits with predictive validity for antipsychotics. The model appears to be able to differentiate first generation from second generation antipsychotics, identify putative antipsychotics with novel mechanisms (i.e., peptides) and reasonably model the therapeutic time course of antipsychotic drugs in humans.
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PMID:The effects of chronic administration of established and putative antipsychotics on natural prepulse inhibition deficits in Brattleboro rats. 1755 53

Rodents treated with N-methyl-D-aspartate (NMDA) antagonists have been thought to be an animal model of schizophrenia. In this study, we examined gene expression in the amygdala of rats chronically treated with MK-801, as well as behavioral changes, such as social behavior, in these animals. The social interaction test, a measure of social behavior, and locomotor activity was performed in male Wistar rats injected with MK-801 (0.13 mg/kg i.p.) or saline for 14 days. Changes in mRNA levels were analyzed using a GeneChip microarray system. Real-time quantitative PCR (RT-qPCR) assay was subsequently conducted to confirm the results of the microarray analysis. MK-801 decreased social interaction and increased locomotor activity in rats, consistent with previous reports. We found 23 downregulated genes and 16 upregulated genes, with the gene encoding arginine-vasopressin (AVP) being most downregulated, and that for transthyretin (Ttr) most upregulated. mRNA levels, quantified by RT-qPCR assay, were altered for genes related to neuropeptides (AVP, Sstr2), the arachidonic cascade (Ptgds), myelination (Mobp, Enpp2), neurotrophic factors (Igfbp2), and hormonal milieu (Ttr). Downregulation of the AVP gene in the amygdala of MK-801-treated rats may provide a basis for the ability of AVP-analogues to ameliorate the behavioral disturbances caused by blockade of the NMDA receptor. The results of this study provide an insight into the neural substrates responsible for the generation of psychotic symptoms.
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PMID:Effect of MK-801 on gene expressions in the amygdala of rats. 1794 90

We report a case of hyponatremia in a patient that occurred 3 days after initiation of treatment with aripiprazole. The patient was a 50-year-old man admitted to an inpatient psychiatric unit for exacerbation of schizophrenia. He was started on aripiprazole and developed hyponatremia that resolved when the medication was stopped. We postulate that the hyponatremia was due to an aripiprazole-induced syndrome of inappropriate secretion of antidiuretic hormone. There have been numerous case reports in the literature of hyponatremia in the literature associated with atypical antipsychotics. We caution clinicians to be aware that the potential hyponatremic-inducing effects of atypical antipsychotics can occur rapidly after initiation of the medications.
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PMID:Antipsychotic-induced hyponatremia: case report and literature review. 1880 26

Brattleboro (BRAT) rats are a mutant variant of the Long-Evans (LE) strain deficient in the neurohormone vasopressin. BRAT rats show behavioural alterations relevant to schizophrenia. In particular, BRAT rats show deficits in prepulse inhibition (PPI) and alterations in various measures of cognition. The aim of this study was to replicate the reported PPI deficits in BRAT rats and its reversal by antipsychotic drugs and to investigate other behavioural and neurochemical characteristics. Acoustic startle reactivity, PPI, spontaneous and amphetamine-induced locomotor activity (LMA) and ex-vivo steady state neurochemistry were measured in male homozygous BRAT rats and LE rats. The effects of antipsychotics on PPI deficits were also determined. Relative to LE, BRAT rats showed enhanced startle reactivity, hyperactivity to a novel environment, PPI deficits and decreased levels of dopamine and DOPAC (dihydroxyphenylacetic acid) in the frontal cortex. BRAT and LE rats showed similar levels of hyperactivity following amphetamine (0.26 mg/kg s.c.). PPI deficits were attenuated by acute clozapine (5-10 mg/kg s.c.), risperidone (0.1-1 mg/kg i.p.), haloperidol (0.1-0.5 mg/kg p.o.) and less robustly by olanzapine (0.3-3 mg/kg s.c.). Chronic administration of clozapine (5 mg/kg s.c., once daily) attenuated baseline hyperactivity and elevated PPI of both strains. Clozapine concentrations were higher in BRAT brains compared with LE rats. These data confirm the reported PPI deficit in BRAT rats and its reversal by antipsychotic drugs, suggesting BRAT rats may represent a potential model for identifying novel antipsychotic drugs.
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PMID:Further neurochemical and behavioural investigation of Brattleboro rats as a putative model of schizophrenia. 1920 63

Mice lacking a functional vasopressin 1b receptor (Avpr1b) display decreased levels of aggression and social memory. Here, we used Avpr1b-knock-out (Avpr1b(-/-)) mice to examine whether an abnormality of this receptor results in specific cognitive deficits in the domain of hippocampal function. Avpr1b(-/-) mice were deficient in sociability and in detecting social novelty, extending previous findings of impairment in social recognition in these mutants. Avpr1b(-/-) mice could recognize previously explored objects and remember where they were experienced, but they were impaired in remembering the temporal order of presentation of those objects. Consistent with this finding, Avpr1b(-/-) mice were also impaired on an object-odor paired associate task that involved a temporal discontiguity between the associated elements. Finally, Avpr1b(-/-) mice performed normally in learning a set of overlapping odor discriminations and could infer relationships among odors that were only indirectly associated (i.e., transitive inference), indicating intact relational memory. The Avpr1b is expressed at much higher levels than any other part of the brain in the pyramidal cells of hippocampal CA2 area, a subfield of the hippocampus that has physiological and genetic properties that distinguish it from subfields CA1 and CA3. The combined results suggest that the Avpr1b, perhaps in CA2, may play a highly specific role in social behavior and episodic memory. Because schizophrenia and bipolar disorder are associated with a unique pathology in CA2 and impairments in both social behavior and episodic memory, this animal model could provide insights into the etiology of these disorders.
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PMID:Vasopressin 1b receptor knock-out impairs memory for temporal order. 1926 62


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