Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In addition to its role in blood vessel and macrophage function, nitric oxide (NO) is a neurotransmitter found in high densities in emotion-regulating brain regions. Mice with targeted disruption of neuronal NO synthase (nNOS) display grossly normal appearance, locomotor activity, breeding, long-term potentiation and long-term depression. The nNOS- mice are resistant to neural stroke damage following middle cerebral artery ligation. Although CO2-induced cerebral vasodilatation in wild-type mice is NO-dependent, in nNOS- mice this vasodilation is unaffected by NOS inhibitors. Establishing a behavioural role for NO has, until now, not been feasible, as NOS inhibitor drugs can only be administered acutely and because their pronounced effects on blood pressure and other body functions obfuscate behavioural interpretations. We now report a large increase in aggressive behaviour and excess, inappropriate sexual behaviour in nNOS- mice.
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PMID:Behavioural abnormalities in male mice lacking neuronal nitric oxide synthase. 747 65

Nitric oxide (NO), produced by either constitutive or inducible isoforms of NO synthase (cNOS or iNOS), influences myocardial inotropic and chronotropic responses. This pathway has been studied using NO donors or NOS inhibitors or by immune-mediated stimulation of iNOS. Although inhibition of constitutive NO activity in the heart does not influence indices of myocardial contractility, NO donors, in some species and preparations, may exert a negative inotropic effect as well as an enhancement of diastolic relaxation. The best documented cardiac action of NO is inhibition of the positive inotropic and chronotropic responses to beta-adrenergic receptor stimulation. Basal NO production, presumable via cNOS, appears to exert a mild tonic inhibition of beta-adrenergic responses. On the other hand, excessive NO production mediated by iNOS may contribute to the myocardial depression and beta-adrenergic hyporesponsiveness associated with conditions such as sepsis, myocarditis, cardiac transplant rejection, and dilated cardiomyopathy. Muscarinic cholinergic stimulation of the heart appears to stimulate NO production that mediates, at least partially, parasympathetic slowing of heart rate and inhibition of beta-adrenergic contractility. NO-stimulated production of 3',5'-cyclic guanosine monophosphate via guanylyl cyclase accounts for many of the observed physiological actions of NO. 3',5'-Cyclic guanosine monophosphate inhibits the beta-adrenergic-stimulated increase in the slow-inward calcium current and reduces the calcium affinity of the contractile apparatus, actions that could contribute to a negative inotropic effect, an abbreviation of contraction, and an enhancement of diastolic relaxation. Biochemical, immunocytochemical, and molecular biological techniques have been used to show the presence of both cNOS and iNOS within the myocardium. cNOS is expressed in myocytes, endothelial cells, and neurons in the myocardium, and there is evidence for iNOS in myocytes, small vessel endothelium, vascular smooth muscle cells, and immune cells that infiltrate the heart. Taken together, these observations suggest that NO influences normal cardiac physiology and may play an important role in the pathophysiology of certain disease states associated with cardiac dysfunction.
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PMID:Role of nitric oxide in the regulation of myocardial function. 756 4

Standard tricyclic antidepressant (TCA) treatment usually entails response latencies of 2 to 4 weeks. To accelerate the antidepressant response, methylphenidate (MPH) was administered together with standard antidepressants in an open label trial. Twenty inpatients (9 females, 11 males) met DSM-III-R criteria for major depressive episode (15 unipolar and 2 bipolar), depression NOS (n = 2), or Research Diagnostic Criteria for schizoaffective illness, depressed type (n = 1). Following evaluation for depression, patients received an open-label oral MPH stimulation trial (MST), in 1 or 2 dosages of 5 to 15 mg at 0900 and 1000 hours. Twenty patients with positive MST response were treated with TCAs combined with MPH (5-15 mg/d). Therapeutic response was defined as 50 percent decline in the Hamilton Rating Scale for Depression. Six of 20 (30%) patients responded after 1 week of combination TCA-MPH, and 10 of 16 (63%) after 2 weeks. Adverse effects of the combination treatment included: dizziness and orthostatic blood pressure changes (n = 3), dry mouth (n = 3), increased anxiety (n = 3), and hypomania (n = 1). The severity of adverse effects required cessation of the MPH in 3 patients. Elevated self-ratings of anxiety were associated with lack of improvement after both 1 and 2 weeks. Adjunctive MPH appears to accelerate response to tricyclics in this systematically conducted open trial, and adverse effects of the TCA-MPH combination were usually tolerable. Positive response on the MST may be predictive of beneficial therapeutic outcome, especially in depressed patients without high anxiety levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The antidepressant response to tricyclics in major depressives is accelerated with adjunctive use of methylphenidate. 783 49

NO donors were found to reduce the rate of Ca2+ release from isolated skeletal muscle sarcoplasmic reticulum (SR) and the open probability of single ryanodine receptor Ca2+ release channels (RyRCs) in planar lipid bilayers, and these effects were prevented by the NO quencher hemoglobin and reversed by 2-mercaptoethanol. Ca2+ release assessed in skeletal muscle homogenates was also reduced by NO that was generated in situ from L-arginine by endogenous, nitro-L-arginine methylester-sensitive NO-synthase. The effect of NO on the RyRC might explain NO-induced depression of contractile force in striated muscles and, since both RyRC isoforms and NOS isoenzymes aer ubiquitous, may represent a wide-spread feedback mechanism in Ca2+ signaling; i.e. Ca-dependent activation of NO production and NO-evoked reduction of Ca2+ release from intracellular Ca2+ stores.
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PMID:Inhibition of the skeletal muscle ryanodine receptor calcium release channel by nitric oxide. 860 45

The membrane-permeant gas NO is a putative intercellular messenger that has been proposed on the basis of previous in vitro studies to be involved in synaptic plasticity, especially the induction of long-term potentiation (LTP) of excitatory synaptic transmission in the hippocampus and cortex. In the present study, the role of NO in synaptic plasticity has been investigated in vivo. In particular, the action of the novel and selective neuronal NO synthase (nNOS) inhibitor 7-nitro-indazole (7-NI) has been investigated on the induction of LTP and depotentiation (DP) of field EPSPs in CA1 of the hippocampus in vivo. Unlike previously studied nonselective NOS inhibitors, 7-NI does not increase arterial blood pressure. In vehicle-injected rats, high-frequency stimulation consisting of a series of trains at 200 Hz induced LTP. However, LTP induction was strongly inhibited in 7-NI (30 mg/kg, i.p.)-treated animals. The inhibitory effect of 7-NI on the induction of LTP was prevented by pretreatment with L-arginine, the substrate amino acid used by NOS. In control animals, low-frequency stimulation consisting of 900 stimuli at 10 Hz induced DP of previously established LTP, whereas in 7-HI-treated animals only a short-term depression was induced. This effect of 7-NI also was prevented by D-arginine. The LTP and DP induced in control animals in this study were NMDA receptor-dependent, the NMDA receptor antagonist 3-(R,S)-2-carboxypiperazin-4-yl-propyl-1- phosphonic acid inhibiting the induction of both forms of synaptic plasticity. The present experiments are the first to demonstrate that an NOS inhibitor blocks the induction of the synaptic component of LTP and DP in vivo and, therefore, these results strengthen evidence that the production of NO is necessary for the induction of LTP and DP.
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PMID:The selective neuronal NO synthase inhibitor 7-nitro-indazole blocks both long-term potentiation and depotentiation of field EPSPs in rat hippocampal CA1 in vivo. 861 7

We examined the relationship between dissociative symptoms and other Axis I and Axis II symptoms among a sample of 53 women diagnosed as having anorexia nervosa (n = 18), bulimia nervosa (n = 27), or eating disorder NOS (n = 8). Dissociative symptoms were measured by the Dissociative Experiences Scale and the dissociation scale from the Trauma Symptom Checklist 40. Severity of dissociative symptoms was generally unrelated to severity of bulimic or anorexic symptomatology but was significantly associated with severity of anxiety and depression. In terms of Axis II symptoms, dissociative symptoms were most highly correlated with schizotypal symptomatology (r = .59), uncorrelated with borderline or antisocial symptomatology, and slightly negatively correlated with histrionic symptomatology.
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PMID:Correlates of dissociative symptoms among women with eating disorders. 874 66

The present study attempted to examine possible gender differences in the vulnerability to depression, specifically with regard to eliciting factors, marital status, age of onset, season of hospitalization, and type of treatment. The records of all patients (67 women and 34 men), treated during 1991 for major depression, dysthymia, or depression NOS at a psychiatric hospital in Southeastern Sweden were examined, and placed in empirically derived categories regarding eliciting factors. The results indicated significant gender differences with regard to eliciting factors, marital status, and age. The eliciting factor in female depression was most commonly "threat to social bonds" whereas in male depression it was "threat to self esteem" or "threat to self respect". Married women were more prone to depression than were married men, as were men living alone compared to women living alone. Women above 60 years of age were significantly more prone to depression than were men of this age group. The results were discussed from two theoretical perspectives: gender role theory and gender-specific developmental theory.
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PMID:Gender differences in the development of depression. 885 96

Veratridine blocks Na(+)-channel inactivation and causes a persistant Na(+)-influx. Exposure of hippocampal slices to 10 microM veratridine led to a failure of synaptic transmission, repetitive spreading depression (SD)-like depolarizations of increasing duration, loss of Ca(+)-homeostasis, a large reduction of membrane potential, spongious edema and metabolic failure. Normalization of the amplitude of the negative DC shift evoked by high K+ ACSF 80 min after veratridine exposure was taken as the primary endpoint for neuroprotection. Compounds whose mechanisms of action includes Na(+)-channel modulation were neuroprotective (IC50-values in microM): tetrodotoxin 0.017, verapamil 1.18, riluzole 1.95, lamotrigine > or = 10, and diphenylhydantoin 16.1. Both NMDA (MK-801 and PH) and non-NMDA (NBQX) excitatory amino acid antagonists were inactive, as were NOS-synthesis inhibitor (nitro-L-arginine and L-NAME) Ca(2+)-channel blockers (cadmium, nimodipine) and a K(+)-channel blocker (TEA). Lubeluzole significantly delayed in time before the slices became epileptic, postponed the first SD-like depolarization, allowed the slices to better recover their membrane potential after a larger number of SD-like DC depolarizations, preserved Ca2+ and energy homeostasis, and prevented the neurotoxic effects of veratridine (IC50-value 0.54 microM). A concentration of lubeluzole, which was 40 x higher than its IC50-value for neuroprotection against veratridine, had no effect on repetitive Na(+)-dependent action potentials induced by depolarizing current in normal ACSF. The ability of lubeluzole to prevent the pathological consequences of excessive Na(+)-influx, without altering normal Na(+)- channel function may be of benefit in stroke.
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PMID:Altered Na(+)-channel function as an in vitro model of the ischemic penumbra: action of lubeluzole and other neuroprotective drugs. 903 12

Induction of the inducible isoform of nitric oxide (NO) synthase (iNOS) in the myocardium is implicated as a mechanism in the development of cardiac depression in immune activated states associated with an enhanced release of cytokines, such as septic shock. We evaluated the in vivo synthesis of NO and tetrahydrobiopterin (BH4), a cofactor of NOS, in the heart tissue using a model of LPS injection in rats (LPS: 10 mg/kg, i.v.). In control rats, iNOS activity or iNOS mRNA in the heart was negligible. Three hours after LPS administration, a marked induction of iNOS mRNA and activity was observed in the heart. A significant increase in BH4 content and GTP cyclohydrolase mRNA abundance was also observed in the heart from LPS-treated rats. Our results demonstrate induction of NO synthesis and parallel increase in BH4 concentration in the heart of rats after LPS treatment in vivo and may provide molecular evidence responsible for the increased production of BH4 which may up-regulate iNOS activity in the heart in vivo.
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PMID:Co-induction of nitric oxide and tetrahydrobiopterin synthesis in the myocardium in vivo. 904 35

Depressed (n = 14) and remitted (n = 9) patients with mood disorder, patients with depressive disorder not otherwise specified (NOS; n = 10) and normal subjects (n = 8) underwent non-invasive and quantitative measurement of cerebral blood flow using HMPAO and SPECT in a resting state. The mean and regional cerebral blood flow (CBF) in twelve ROIs were compared among the four groups and correlations between CBF and the depressive symptoms were studies. The CBF was computed using graphical analysis on the SPECT console after a bolus injection of Tc-99m HMPAO and radionuclide angiography. The depressed group had significantly lower mCBF in the bilateral hemisphere and rCBF in all except one of the ROIs than the NOS and normal group. Significant negative correlations were found between the Hamilton scale for depression and rCBF in the bilateral lower frontal cortex after correcting for age in the mood disorder. Parallel analysis using both the quantitative and semiquantitative methods revealed that the former provided more global reduction of CBF in mood disorder. These results indicate that mean and regional CBF measured by this non-invasive method contributes to the objective evaluation of depressive symptoms. Negative correlations between HRSD and rCBF in the frontal regions indicate that frontal hypoactivity is closely related to depressive symptoms.
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PMID:Quantitative regional cerebral flow measured by Tc-99M HMPAO SPECT in mood disorder. 910 61


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