排序方式: 共有58条查询结果,搜索用时 15 毫秒
1.
Rebeca Vidal† Elsa M. Valdizán† Ricardo Mostany Angel Pazos† Elena Castro† 《Journal of neurochemistry》2009,110(3):1120-1127
The mode of action of antidepressant drugs may be related to mechanisms of monoamines receptor adaptation, including serotonin 5-HT4 receptor subtypes. Here we investigated the effects of repeated treatment with the selective serotonin reuptake inhibitor fluoxetine for 21 days (5 and 10 mg/kg, p.o., once daily) on the sensitivity of 5-HT4 receptors by using receptor autoradiography, adenylate cyclase assays and extracellular recording techniques in rat brain. Fluoxetine treatment decreased the density of 5-HT4 receptor binding in the CA1 field of hippocampus as well as in several areas of the striatum over the doses of 5–10 mg/kg. In a similar way, we found a significant lower response to zacopride-stimulated adenylate cyclase activity in the fluoxetine 10 mg/kg/day treated group. Furthermore, post-synaptic 5-HT4 receptor activity in hippocampus-measured as the excitatory action of zacopride in the pyramidal cells of CA1 evoked by Schaffer collateral stimulation was attenuated in rats treated with both doses of fluoxetine. Taken together, these results support the concept that a net decrease in the signalization pathway of 5-HT4 receptors occurs after chronic selective serotonin reuptake inhibitor treatment: this effect may underlie the therapeutic efficacy of these drugs. 相似文献
2.
Margarita Kirkova Elina Tzvetanova Stefani Vircheva Rositsa Zamfirova Beata Grygier Marta Kubera 《Cell biochemistry and function》2010,28(6):497-502
In vivo effects of the antidepressant fluoxetine on spleen antioxidant status of C57BL/6 mice were studied using a melanoma experimental model. After a 14‐day treatment with fluoxetine (10 mg kg?1 day?1, i.p.), the endogenous antioxidant non‐enzyme (glutathione) and enzyme (superoxide dismutase (SOD) and glutathione peroxidase (GPx)) defense systems in spleen of healthy animals were not changed; the lipid peroxidation (LP) was also unchanged. When B16F10 melanoma cells were introduced in C57BL/6 mice 2 h before fluoxetine treatment, a drug‐protective effect against the melanoma‐induced oxidative changes (increased LP and decreased total glutathione (GSH)‐level, as well as antioxidant enzyme activities) in spleen was observed. Fluoxetine dose‐dependently reduced the amounts of free oxygen radicals (hydroxyl and superoxide anion radicals), generated in chemical systems. Taken together, the present results suggest that fluoxetine, acting as antioxidant, prevents from melanoma‐induced oxidative changes in mice spleen. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
3.
1. AMPA receptor potentiators (ARPs) exhibit antidepressant-like activity in preclinical tests (for example, the forced swim test) that are highly predictive of efficacy in humans. Unlike most currently used antidepressants, ARPs do not elevate extracellular levels of biogenic amines (e.g., 5HT, NE) in prefrontal cortex at doses that are active in the forced swim test.2. The present series of experiments examined the effects of combining the ARP, LY 392098, with biogenic amine-based antidepressants in the forced swim test. Male, NIH Swiss mice were placed in a cylinder of water and observed for attempted escape behaviors and immobility.3. LY 392098 dose-dependently decreased immobility as did a range of classical antidepressants. At doses of LY 392098 below those that decreased immobility, this compound significantly increased the potency with which fluoxetine and citalopram (SSRI antidepressants), imipramine (tricyclic antidepressant), duoxetine (norepinephrine/serotonin uptake blocker), nisoxetine (norepinephrine uptake inhibitor), and rolipram (PDE4 inhibitor) decreased immobility in the forced swim test with potency shifts upward of 5-fold (fluoxetine, imipramine, and rolipram). Likewise, ineffective doses of the traditional antidepressants potentiated the effects LY 392098 with shifts in the dose-effect functions that were 10-fold or more for citalopram, fluoxetine, imipramine, and duloxetine.4. Combined with other evidence for a role of AMPA receptors in the efficacy of antidepressants, the current data suggest that the addition of an ARP may augment the activity and perhaps the onset of the therapeutic effects of biogenic amine and second messenger-based antidepressants. 相似文献
4.
Keren Ofek Karl Schoknecht Naomi Melamed‐Book Uwe Heinemann Hermona Soreq 《Journal of cellular and molecular medicine》2012,16(11):2736-2744
Ischaemic stroke patients treated with Selective Serotonin Reuptake Inhibitors (SSRI) show improved motor, cognitive and executive functions, but the underlying mechanism(s) are incompletely understood. Here, we report that cerebral arterioles in the rat brain superfused with therapeutically effective doses of the SSRI fluoxetine showed consistent, dose‐dependent vasodilatation (by 1.2 to 1.6‐fold), suppressible by muscarinic and nitric oxide synthase (NOS) antagonists [atropine, NG‐nitro‐l ‐arginine methyl ester (l ‐NAME)] but resistant to nicotinic and serotoninergic antagonists (mecamylamine, methylsergide). Fluoxetine administered 10–30 min. following experimental vascular photo‐thrombosis increased arterial diameter (1.3–1.6), inducing partial, but lasting reperfusion of the ischaemic brain. In brain endothelial b.End.3 cells, fluoxetine induced rapid muscarinic receptor‐dependent increases in intracellular [Ca2+] and promoted albumin‐ and eNOS‐dependent nitric oxide (NO) production and HSP90 interaction. In vitro, fluoxetine suppressed recombinant human acetylcholinesterase (rhAChE) activity only in the presence of albumin. That fluoxetine induces vasodilatation of cerebral arterioles suggests co‐promotion of endothelial muscarinic and nitric oxide signalling, facilitated by albumin‐dependent inhibition of serum AChE. 相似文献
5.
Dose-dependent neurotoxic effects (decrease in the amplitude of field potentials generated by neurons of the СА1 area, dentate gyrus, and dorsal striatum, but not by neurons of layers ІІ and ІІІ of the parietal cortex, recorded in slices
of the rat brain) were observed 24 h after i.p. injection оf dexamethasone in doses of 7 and 20 mg/kg. Dexamethasone-induced
decreases in the reactivity of glutamatergic synapses in the studied cerebral structures were weakened by a noncompetitive
blocker of NMDA receptors, ketamine (30 mg/kg), and an inhibitor of tyrosine protein phosphatases, sodium vanadate (15 mg/kg),
if the latter agent was injected 6 h after dexamethasone administration. The neurotoxic effect of dexamethasone was intensified
by a coagonist of NMDA receptors, glycine (50 mg/kg), as well as in the case where injections of dexamethasone were combined
with single injections of the antidepressant fluoxetine (20 mg/kg) but not when another antidepressant, pyrazidol, was injected
in the same dose. Chronic (two weeks) injections of fluoxetine and pyrazidol weakened manifestations of dexamethasone neurotoxicity.
On-regulation of NMDA receptors and suppression of expression of neurotrophins are considered probable mechanisms underlying
neurotoxicity of this hormone. The effect of chronic injections of antidepressants on the respective processes is discussed.
Neirofiziologiya/Neurophysiology, Vol. 40, No. 4, pp. 312–231, July–August, 2008. 相似文献
6.
Arantza Gutirrez Gonzalo Saracíbar Luis Casis Enrique Echevarría Víctor Manuel Rodríguez Maria Teresa Macarulla Luis C. Abecia María P. Portillo 《Obesity (Silver Spring, Md.)》2002,10(6):532-540
Objective: The aim of this work was to study the potential involvement of neuropeptide Y (NPY) and orexins in the anorexigenic mechanism of fluoxetine in obese Zucker rats, assessing the effects of chronic fluoxetine treatment on NPY and orexin immunostaining in several hypothalamic regions. Research Methods and Procedures: Male obese Zucker (fa/fa) rats were administered fluoxetine (10 mg/kg intraperitoneally) daily for 2 weeks. The control group was administered 0.9% NaCl solution. Carcass composition was assessed using the official methods of the Association of Official Analytical Chemists. To test the potential thermogenic effect of fluoxetine administration, total body oxygen consumption was measured daily for 60 minutes before fluoxetine or saline injection and for 30 minutes after drug or saline injection. Hypothalamic arcuate and paraventricular nuclei, and the lateral hypothalamic area were immunostained for NPY, orexin A, and orexin B. Commercial kits were used for serum determinations. Results: Chronic fluoxetine administration in obese Zucker rats generated a reduction in body weight gain, food intake, adipocyte size, fat mass, and body protein. A decrease in NPY immunostaining in the paraventricular nucleus, without changes in the arcuate, was observed. However, no changes were observed in the number of neural cells immunostained for orexin A or orexin B in the lateral hypothalamic area. Discussion: Due to the hyperphagic effect of NPY in the paraventricular nucleus, these results suggest that NPY, but not orexins, could be involved in the anorexigenic effect of fluoxetine in obese Zucker rats. 相似文献
7.
In albino rats anesthetized with urethane, most medial raphe neurons are characterized by a low rate of the discharges. Acute immobilization stress resulted in a significant enhancement in the number of regularly discharging neurons. After immobilization, the number of neurons with a low-rate impulsation decreased, while the number of neurons with intensive firing increased. Treatment with fluoxetine enhanced the number of regularly firing neurons more than three times, and a predominant part of the neurons demonstrated a high level of background activity. It should be supposed that a significant part of the neurons with high-rate discharges are serotonergic, because their number also increased after fluoxetine administration. 相似文献
8.
E. Hara P.S. Reinach Q. Wen P. Iserovich J. Fischbarg 《The Journal of membrane biology》1999,171(1):75-85
We have studied regulatory volume responses of cultured bovine corneal endothelial cells (CBCEC) using light scattering.
We assessed the contributions of fluoxetine (Prozac) and bumetanide-sensitive membrane ion transport pathways to such responses
by determining K+ efflux and influx. Cells swollen by a 20% hypo-osmotic solution underwent a regulatory volume decrease (RVD) response, which
after 6 min restored relative cell volume by 98%. Fluoxetine inhibited RVD recovery; 20 μm by 26%, and 50 μm totally. Fluoxetine had a triphasic effect on K+ efflux; from 20 to 100 μm it inhibited efflux 2-fold, whereas at higher concentrations the efflux first increased to 1.5-fold above the control value,
and then decreased again. Cells shrunk by a 20% hyperosmotic solution underwent a regulatory volume increase (RVI) which also
after 6 min restored the cell volume by 99%. Fluoxetine inhibited RVI; 20 μm by 25%, and 50 μm completely. Bumetanide (1 μm) inhibited RVI by 43%. In a Cl−-free medium, fluoxetine (50–500 μm) progressively inhibited bumetanide-insensitive K+ influx. The inhibitions of RVI and K+ influx induced by fluoxetine 20 to 50 μm were similar to those induced by 1 μm bumetanide and by Cl−-free medium. A computer simulation suggests that fluoxetine can interact with the selectivity filter of K+ channels. The data suggest that CBCEC can mediate RVD and RVI in part through increases in K+ efflux and Na-K-2Cl cotransport (NKCC) activity. Interestingly, the data also suggest that fluoxetine at 20 to 50 μm inhibits NKCC, and at 100–1000 μm inhibits the Na+ pump. One possible explanation for these findings is that fluoxetine could interact with K+-selective sites in K+ channels, the NKC cotransporter and the Na+ pump. 相似文献
9.
Gould GG Hensler JG Burke TF Benno RH Onaivi ES Daws LC 《Journal of neurochemistry》2011,116(2):291-303
BTBR mice are potentially useful tools for autism research because their behavior parallels core social interaction impairments and restricted-repetitive behaviors. Altered regulation of central serotonin (5-HT) neurotransmission may underlie such behavioral deficits. To test this, we compared 5-HT transporter (SERT), 5-HT(1A) and 5-HT(2A) receptor densities among BTBR and C57 strains. Autoradiographic [(3) H] cyanoimipramine (1 nM) binding to SERT was 20-30% lower throughout the adult BTBR brain as compared to C57BL/10J mice. In hippocampal membrane homogenates, [(3) H] citalopram maximal binding (B(max) ) to SERT was 95 ± 13 fmol/mg protein in BTBR and 171 ± 20 fmol/mg protein in C57BL/6J mice, and the BTBR dissociation constant (K(D) ) was 2.0 ± 0.3 nM versus 1.1 ± 0.2 in C57BL/6J mice. Hippocampal 5-HT(1A) and 5-HT(2A) receptor binding was similar among strains. However, 8-OH-DPAT-stimulated [(35) S] GTPγS binding in the BTBR hippocampal CA(1) region was 28% higher, indicating elevated 5-HT(1A) capacity to activate G-proteins. In BTBR mice, the SERT blocker, fluoxetine (10 mg/kg) and the 5-HT(1A) receptor partial-agonist, buspirone (2 mg/kg) enhanced social interactions. The D(2) /5-HT(2) receptor antagonist, risperidone (0.1 mg/kg) reduced marble burying, but failed to improve sociability. Overall, altered SERT and/or 5-HT(1A) functionality in hippocampus could contribute to the relatively low sociability of BTBR mice. 相似文献
10.
Neonatal treatment with fluoxetine improves mitochondrial respiration and reduces oxidative stress in liver of adult rats
下载免费PDF全文
![点击此处可从《Journal of cellular biochemistry》网站下载免费的PDF全文](/ch/ext_images/free.gif)