The novel and conventional conditions were matched for doze probability (a measure of predictability based on the sentence context), lexical association between the sentence frame and the final word (using latent semantic analysis), and other factors known to influence ERPs to language stimuli. To compare effects of novelty to previously reported effects of predictability, Protein Tyrosine Kinase inhibitor a high-doze conventional condition (“”The only way to get around Venice is to navigate the canals in a boat.”") was included. ERPs were time-locked

to sentence final words (“”boat”") presented in either the left visual field, to preferentially stimulate the RH (Ivf/RH), or in the right visual field, targeting the LH (rvf/LH). The N400 component of the ERP was affected by predictability in both presentation sides, but by novelty only in rvf/LH. Two distinct late frontal positive effects were observed. Word predictability modulated a frontal positivity with a LH focus, but semantic novelty modulated a frontal positivity focused in RH. This is the first demonstration that the frontal positivity may be composed of multiple overlapping components with distinct functional and anatomical characteristics. Extending contemporary accounts of the frontal positivity,

we suggest that both frontal positivities reflect learning Selleck Barasertib mechanisms involving prediction based on statistical regularities in language Monoiodotyrosine (LH) and world knowledge (RH). Published by Elsevier Ltd.”
“There

is considerable evidence of circadian rhythm abnormalities in mood disorders. Morningness-eveningness, the degree to which people prefer organizing their activity and sleep patterns toward the morning or evening, is related to circadian phase and is associated with mood, with relatively greater psychological distress among evening types. Given that circadian rhythms may also relate to the Behavioral Activation System (BAS) and positive affect (PA), but not to the Behavioral Inhibition System (BIS) or negative affect (NA), it was hypothesized that individual differences in BAS sensitivity and levels of PA, but not BIS and NA, would explain the association between morningness-eveningness and depression in a sample of 208 individuals with a range of depressive symptomatology. As predicted, increasing eveningness was associated with greater depression, lower BAS, and lower PA, but not directly associated with NA. Path analyses supported a model wherein morningness-eveningness is associated with depression via multi-step indirect paths including BAS-Reward Responsiveness, PA, and NA. A path between BIS and depression was distinct from the one involving morningness-eveningness. A variety of alternative path models all provided a weaker fit to the data.

Here, the in vivo neuroprotective effect of riluzole on the intrinsic activity of Purkinje cells (PCs) in a rat model of cerebellar ataxia induced by 3-acetylpyridine (3-AP) was studied.

Behavioural assessment tests, histological examination and whole cell patch clamp recording

under current clamp conditions were used to explore the possible protective effect of riluzole against induction of ataxia with 3-AP treatment.

Combined treatment with riluzole and 3-AP not only almost completely prevented the neuronal degeneration in cerebellar Purkinje cells layer but also the development of ataxia, which occurred following injection of 3-AP alone and partially improved see more the IPI145 motor behaviour in comparison with ataxic rats. The normal firing behaviour and action potential characteristics of Purkinje

neurones were preserved. The amplitude of both fast after hype rpolarization potential (fAHP) and post train after hyperpolarization potential, a marker of slow AHP (sAHP), along with the duration of post train AHP, which play an important role in regulating the firing behaviour were restored to the control conditions. These findings suggest that riluzole-induced neuroprotection may be mediated at least in part by activation of Ca(2+)-dependent K(+) channel function. (C) 2009 Elsevier Inc. All rights reserved.”
“Tissue-type plasminogen activator (tPA) is the only drug approved for the treatment of thromboembolic stroke, but it might lead to some neurotoxic side effects. tPA is a highly specific serine proteinase, one. of the two principal plasminogen activators and one of the three trypsin-like serine proteinases of the tissue kallikrein family. We have observed that tPA injection

in the SN leads to the degeneration of the dopaminergic neurons in a dose-dependent manner, without affecting the GABAergic neurons. We also found that tPA injected in the substantia nigra of rats produced the disruption of the blood-brain barrier (BBB) integrity, the induction of microglial activation, the loss of astroglia and the expression of aquaporin 4 (AQP4), as well as an increase in the expression of NMDA receptors and the brain derived neurothrophic factor (BDNF). All these effects, along with DOCK10 the changes produced in the phosphorylated forms of several MAP kinases and the transcription factor CREB, and the increase in the expression of nNOS and iNOS observed under our experimental conditions, could be involved in the loss of dopaminergic neurons. (C) 2009 Elsevier Inc. All rights reserved.”
“The central nervous system (CNS) appears to be the critical target of manganese (Mn), and neurotoxicity has been the focus of most of the health effects of manganese. In brain, the mechanism underlying the Mn-induced cell death is not clear.

“
“Tremendous advances in our understanding of pathogenesis of amyotrophic lateral sclerosis (ALS) have provided a

rich pipeline of drugs for clinical trialists. At least 32 unique compounds have been tested. Nevertheless, riluzole is currently the only treatment that prolongs survival. We present a critical overview of past clinical trials, how therapies are selected for testing in people, challenges with ALS clinical trial design and conduct, and ways to best move forward.”
“This review focuses Selonsertib on recent data regarding inflammatory demyelinating neuropathies and neuropathies associated with monoclonal gammopathies. We describe both acute and chronic inflammatory neuropathies, and we discuss conditions ranging from mostly cell-mediated to antibody-mediated disorders. These diseases are characterized

by proximal and distal sensory motor involvement. Treatments are based on immune-modulation and/or immune-suppression. Work-up sequence and therapeutical modes are discussed in the light of recently published data, with a special interest on new treatment modalities.”
“Myasthenia gravis (MG) is a prototypic antibody-mediated neurological autoimmune disorder. Herein we characterize modern treatment algorithms that are adapted to disease severity, and introduce the current principles of escalating strategies for MG treatment. In non-thymoma patients younger than about 50 years of age and with generalized weakness, a complete early (but not AMP deaminase urgent) Selleckchem Roscovitine thymectomy is considered as state-of-the-art on the basis of circumstantial evidence and expert opinion. In up to 10% of patients, MG is associated with a thymoma (i.e., is of paraneoplastic origin). The best surgical type of procedure is still under debate.

Myasthenic crisis is best treated by plasmapheresis, mostly

combined with immunoabsorption techniques. Intravenous immunoglobulins are a reasonable alternative, but a shortage in supplies and high prices limit their use. In generalized MG, a wide array of immunosuppressive treatments has been established, although not formally tested in double-blind, prospective trials. With regard to immunosuppression, azathioprine is still the standard baseline treatment, often combined with initial corticosteroids. In rare patients with an inborn hepatic enzyme deficiency of thiomethylation, azathioprine may be substituted by mycophenolate mofetil. Severe cases may benefit from combined immunosuppression with corticosteroids, cyclosporine A, and even with moderate doses of methotrexate or cyclophosphamide. Tacrolimus is under investigation.

In refractory cases, immunoablation via high-dose cyclophosphamide followed by trophic factors such as granulocyte colony-stimulating factor has also been suggested. In the future we may face an increased use of novel, B-cell, or T-cell directed monoclonal antibodies.

With advancing hydrocephalus, expression of AQPs 1 and 4 increased at the brain-CSF

interfaces; AQP1 was localized to the endothelium of cortical capillaries with increased AQP4 expression in surrounding astrocytes end feet. AQP1 expression level was increased in the pia mater, with prominent AQP4 expression in the subpial layers. Citarinostat manufacturer Subependymal capillaries expressed AQP1 in the endothelium, with increasing AQP4 expression in surrounding astrocytes. Hydrocephalic animals (postnatal day 26) had significant nonendothelial (CD34(-)) AQP1 expression in the septal nucleus of the basal forebrain, an area affected by increased intracranial pressure.

CONCLUSION: Biphasic AQP1 expression in the CP with increased AQPs 1 and 4 at the brain-fluid interfaces may indicate compensatory mechanisms to regulate choroidal cerebrospinal fluid secretion and increase parenchymal fluid absorption in the high-pressure hydrocephalic

condition.”
“The N termini of the capsid proteins VP1 and VP2 of adeno-associated find more virus (AAV) play important roles in subcellular steps of infection and contain motifs that are highly homologous to a phospholipase A(2) (PLA(2)) domain and nuclear localization signals (NLSs). To more clearly understand how virion components influence infection, we have generated mutations in these regions and examined their effects on subcellular trafficking, capsid stability, transduction, and sensitivity to pharmacological enhancement. All mutants tested assembled into capsids; retained the correct ratio of VP1, VP2, and VP3; packaged DNA similarly

to recombinant AAV2 (rAAV2); however and displayed similar stability profiles when heat denatured. Confocal microscopy demonstrated that these mutants trafficked through a perinuclear region in the vicinity of the Golgi apparatus, with a subset of mutants displaying more-diffuse localization consistent with an NLS-deficient phenotype. When tested for viral transduction, two mutant classes emerged. Class I (BR1(-), BR2(-), and BR2+K) displayed partial transduction, whereas class II (VP3only, (HD)-H-75/AN, BR3(-), and BR3+K) were severely defective. Surprisingly, one class II mutant (BR3+K) trafficked identically to rAAV2 and accumulated in the nucleolus, a step recently described by our laboratory that occurs with wild-type infection. The BR3+K mutant, containing an alanine-to-lysine substitution in the third basic region of VP1, was 10- to 100-fold-less infectious than rAAV2 in transformed cell lines (such as HEK-293, HeLa, and CV1-T cells), but in contrast, it was indistinguishable from rAAV2 in several nontransformed cell lines, as well as in tissues (liver, brain, and muscle) in vivo. Complementation studies with pharmacological adjuvants or adenovirus coinfection suggested that additional positive charges in NLS regions restrict mobilization in the nucleus and limit transduction in a transformed-cell-specific fashion.

We identified 2,622, 1,434,

and 1,703 polymorphisms in the inoculum and in the two foot lesions, respectively: most of the substitutions occurred in only a small fraction of the population and represented the progeny from recent cellular replication prior to onset of any selective pressures. We estimated the upper limit for the genome-wide mutation rate of the virus within a cell to be 7.8 x 10(-4) per nucleotide. The greater depth of detection achieved by NGS demonstrates that this method is a powerful and valuable tool for the dissection of FMDV populations within hosts.”
“A hallmark of human immunodeficiency virus type 1 (HIV-1) pathogenesis is the rapid loss of CD4 T cells leading to generalized immune dysfunction, including an exhausted CD8 T cell phenotype. Understanding the necessary factors that govern the functional quality and protective potential of antiviral T cell responses would facilitate CHIR-99021 in vitro rational vaccine design and improve therapeutic strategies to combat persistent infections.

Mouse models of chronic viral infection demonstrate that interleukin-21 (IL-21), produced primarily by CD4 T cells, is required for the generation and maintenance of functionally competent CD8 T cells and viral containment. We reasoned that preserved IL-21 production during HIV-1 infection would be associated with enhanced CD8 T cell function, allowing improved viral control. Here we analyzed the ability of CD4 and CD8 T cells to produce several cytokines in addition to IL-21 ex vivo following stimulation with overlapping HIV-1 peptides. Both click here CD4 and CD8 T cells were able to produce IL-21 in response to HIV-1 infection, with the latter cell type more closely associated with viral control. Furthermore, IL-21-producing HIV-1-specific CD4 T cells (compared to those producing other cytokines) were the best indicator of functional CD8 T cells. Our results demonstrate that HIV-1-specific IL-21-producing CD8 T cells are induced following primary infection and enriched in elite controllers, suggesting a critical role for these cells in the maintenance

of viremia control.”
“Most retroviruses express all of their genes from a Cytoskeletal Signaling inhibitor single primary transcript. In order to allow expression of more than one gene from this RNA, differential splicing is extensively used. Cellular quality control mechanisms retain and degrade unspliced or partially spliced RNAs in the nucleus. Two pathways have been described that explain how retroviruses circumvent this nuclear export inhibition. One involves a constitutive transport element in the viral RNA that interacts with the cellular mRNA transporter proteins NXF1 and NXT1 to facilitate nuclear export. The other pathway relies on the recognition of a viral RNA element by a virus-encoded protein that interacts with the karyopherin CRM1. In this report, we analyze the protein factors required for the nuclear export of unspliced foamy virus (FV) mRNA. We show that this export is CRM1 dependent.

In addition, neuronal apoptosis inhibitory protein (NAIP), cIAP1, and

cIAP2 modulate innate immune responses through control of the inflammasome complex. This review examines the role of mammalian IAPs in regulating immunity and describes the implications of a new class of pan-IAP antagonists for the treatment of immune disorders.”
“Confabulation PCI-32765 research buy denotes the emergence of memories of experiences and events which never took place. Whether there are distinct forms with distinct mechanisms is still debated. In this study, we explored 4 forms of confabulation and their mechanisms in 29 amnesic patients. Patients performed tests of explicit memory, executive functions, and two test of orbitofrontal reality filtering (memory selection and extinction capacity in a reversal learning task) previously shown to be strongly associated with confabulations that patients act upon and disorientation. Results indicated the following associations: (1) Intrusions in a verbal memory

test (simple provoked confabulations) dissociated from all other forms of confabulation and were not associated with any specific cognitive measure. (2) Momentary confabulations, defined as confabulatory responses to questions and measured with a confabulation questionnaire, were associated with impaired mental flexibility, a tendency to fill buy SRT2104 gaps in memory, and with one measure of reality filtering. Momentary confabulations, therefore, may emanate from diverse causes. (3) Behaviourally spontaneous confabulation, characterized by confabulations that the patients act upon and disorientation, was strongly associated with failure in the two reality filtering tasks.

Behaviourally spontaneous confabulation may be seen as a specific instance of momentary confabulations with a distinct mechanism. (4) A patient Fludarabine manufacturer producing fantastic confabulations with nonsensical, illogical content had wide-spread cognitive dysfunction and failed in the reality filtering tasks. The results support the presence of truly or partially dissociable types of confabulation with different mechanisms. (C) 2012 Elsevier Ltd. All rights reserved.”
“Infections with variant Creutzfeldt-Jakob disease (vCJD) have almost exclusively occurred in young patients, but the reasons for this age distribution are uncertain. Our data suggest that the pathogenesis of many peripherally acquired transmissible spongiform encephalopathy (TSE) agents is less efficient in aged individuals. Four vCJD cases linked to transfusion of vCJD-contaminated blood or blood products have been described. Three cases occurred in elderly patients, implying that intravenous exposure is more efficient in aged individuals than other peripheral routes. To test this hypothesis, young (6 to 8 weeks old) and aged (600 days old) mice were injected intravenously with a TSE agent. In aged and young mice, the intravenous route was more efficient than other peripheral routes of TSE agent exposure.

Conclusions: Based on our initial data, [C-11]PBR28 PET appears to have potential for imaging of various inflammatory processes involving macrophage activation. (C) 2013 Elsevier Inc. All rights reserved.”
“Objective: The objective of this study was to examine the effect of arterial grafting on long-term coronary artery bypass grafting mortality.

Methods: Consecutive coronary artery bypass grafting surgeries performed at a single tertiary care center between 1995 check details and 2007 were reviewed. Long-term survival was compared among

patients according to the type of arterial grafts used: no internal thoracic artery, single internal thoracic artery, single internal thoracic artery with other arterial graft, or bilateral internal thoracic artery. Cox proportional hazard models were generated to examine the association of arterial grafting with mortality.

Results: A total of 8264 isolated coronary artery bypass grafting operations were performed and followed for a median time of 4.7 years (interquartile range, 2.1-7.5). A single internal thoracic artery was used in the majority of patients (79%), multiple arterial grafts were used in 24% of patients,

and bilateral internal thoracic artery grafts were used in 13% of patients. Patients who received multiple arterial grafts were more likely to be younger, to be male, and to undergo non-urgent surgery. Prostatic acid phosphatase After adjusting for these differences, patients SCH772984 mouse who received bilateral internal thoracic artery grafts were found to have a significant survival advantage when compared with all other patients, including those who received a single internal thoracic artery plus other arterial grafts (hazard ratio, 0.818; confidence interval, 0.672-0.996). Survival at 10 years was 71% for patients with bilateral internal thoracic artery grafts compared with 66% for patients with single internal thoracic artery grafts and 58% for patients with no internal

thoracic artery graft. Patients with bilateral internal thoracic artery grafts had significantly better freedom from readmission for acute coronary syndrome (hazard ratio, 0.802; confidence interval, 0.668-0.963).

Conclusions: After adjusting for relevant clinical differences, only multiple arterial grafting using the bilateral internal thoracic artery was able to offer a long-term survival advantage over single internal thoracic artery grafting in patients undergoing coronary artery bypass grafting. (J Thorac Cardiovasc Surg 2012; 144:1408-15)”
“The fatty acids, n-butyric acid (BA), 4-phenylbutyric acid (PBA) and valproic acid (VPA, 2-propylpentanoic acid) have been used for many years in the treatment of a variety of CNS and peripheral organ diseases including cancer.

Computer simulation models suggest that coordinate spatial relations representations should be easier to encode if one attends to a relatively large region of space, whereas categorical spatial relations should be easier to encode if one attends to a relatively small region of space. We tested these predictions. To vary the scope of attention, we asked participants to focus on the local or global level of Navon letters, and immediately afterwards had them decide whether a dot was within 2.54 cm of a bar (coordinate

judgment) or was above or below the bar (categorical judgment). Participants were faster in the coordinate task after they had just focused on the global level of a Navon letter whereas they were faster in the categorical task after they had just focused on the local level. Although we did not test the hemispheric lateralization of these effects, these findings have direct implications for theories of why the cerebral

hemispheres differ in their relative ease of encoding the two kinds of spatial relations. (C) 2010 Elsevier Ltd. All rights reserved.”
“Objective: We sought to evaluate the feasibility and efficacy of a new type of video-assisted minimally invasive surgery for patients with atrial fibrillation.

Methods: Between December 2006 and February 2008, 81 patients with lone atrial fibrillation (49 with paroxysmal, 17 with persistent, and 15 with long-standing persistent atrial fibrillation) underwent this therapy with a bipolar radiofrequency ablation system. The main surgical procedures included bilateral pulmonary vein antrum isolation, obliteration of the left atrial appendage, division of the ligament of Marshall, and intraoperative electrophysiologic testing.

Results:

The mean operation duration was 2.5 hours. One (1.2%) case was confirmed of left atrial appendage thrombus during the procedure. One (1.2%) patient was converted to sternotomy during the operation. Reintubation occurred in 1 (1.2%) patient, and acute heart failure occurred in 1 (1.2%) patient. One (1.2%) patient died of cerebral infarction 1 month after the operation. Follow-up was done between 3 and 19 months (mean, 12.7 +/- 3.9 months) after the operation. At discharge, 72.5%(58/81) of all patients were in sinus rhythm (paroxysmal atrial fibrillation, 83.7%; persistent atrial fibrillation, 64.7%; and long-standing persistent atrial fibrillation, 40.0%). At 3 months, overall 78.5%(62/79) were in sinus rhythm (paroxysmal atrial fibrillation, 85.7%; persistent atrial fibrillation, 82.4%; and long-standing persistent atrial fibrillation, 46.2%). At 6 months, overall 78.5% (62/79) were in sinus rhythm(paroxysmal atrial fibrillation, 85.7%; persistent atrial fibrillation, 70.6%; and long-standing persistent atrial fibrillation, 61.5%). At 12 months, overall 79.

Male Wistar rats were trained to self-administer ethanol intravenously and received intra-NAc infusions of vehicle or the selective mGluR5 antagonist 3-((2-methyl-1,3-thiazol-4-yl)ethynyl)pyridine (MTEP) alone and in combination with a PKCE > translocation inhibitor (E > V1-2) or a scrambled control peptide (sE > V1-2). The effects of intra-NAc MTEP on food-reinforced responding and open-field locomotor activity

were also determined.

MTEP (1 mu g/mu l) had no effect on ethanol or food reinforcement or locomotor activity when infused into either region. MTEP (3 mu g/mu l) reduced ethanol reinforcement when infused into the NAc shell but not the core, and this effect was reversed by E > V1-2 (1 mu g/mu l) but not sE > V1-2 (1 mu g/mu

l). In both regions, this concentration of MTEP did not alter food-reinforced responding or locomotor activity, and infusion of E > V1-2 Selleckchem Dactolisib alone did not alter ethanol reinforcement. MTEP (10 mu g/mu l) reduced locomotor activity when infused into the shell; therefore, this concentration was not further tested on responding for ethanol or food.

Blockade of mGluR5 receptors in the NAc shell reduces ethanol reinforcement LOXO-101 mouse via a PKCE >-dependent mechanism.”
“According to the simulation theory, the internal simulation of a movement (imagined movement, IM) and its execution (actual movement, AM) are based on the same motor representations. The brain uses these representations for controlling action. The specific objective of this study Adenosine triphosphate was to investigate the updating process of internal models of action in adults, through massive environmental changes involved by microgravity (0G). 0G has multiple effects on motor control, including short-term adaptations with

respect to the planification and performance of actions. However, the effects of 0G on internal representations of action are still largely unknown. To address this issue, thirteen subjects performed first sit-to-stand (STS) and back-to-sit (BTS) tasks, and subsequently had to imagine movement performance in these tasks. The tasks were performed under normogravity (1G) and 0G conditions. Based on durations of actual and IMs, two main results emerged from this study. In 1G, actual and IM’s durations were similar. However, in 0G, AM durations were significantly longer than IM durations. Furthermore, IM durations in 0G were similar to the 1G value. These results show that although the planification and execution of action were immediately adapted to the 0G condition, the storage of afferent information was inadequate to recalibrate the predictive model. These results suggest that sudden change in gravity was not considered for updating internal models of action, and that forward model probably required more practice in order to integrate the modification of the sensorial feedback generated by the new environmental constraints. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Formalin produced a typical pattern of flinching and licking/lifting behaviors. Local peripheral ipsilateral, but not contralateral, pre-treatment with fluoxetine (0.3-3 nmol/paw) increased in a dose-dependent fashion 0.5% formalin-induced nociception. In contrast, intrathecal pretreatment with fluoxetine (0.3-3 nmol/rat) prevented nociception induced by formalin. The peripheral pronociceptive effect of fluoxetine was prevented by the 5-HT2A (ketanserin, 3-10 pmol/paw), 5-HT2B (3-(2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl)-2,4(1H,3H)-quinazolinedione www.selleckchem.com/products/BEZ235.html (+) tartrate, RS-127445, 3-10 pmol/paw), 5-HT2C (8-[5-(2,4-dimethoxy-5-(4-trifluoromethylphenylsulphonamido)

phenyl-5-oxopentyl]1,3,8-triazaspiro[4.5] decane-2,4-dione hydrochloride, RS-102221, 3-10 pmol/paw), 5-HT3 (ondansetron, 3-10 nmol/paw), 5-HT4 ([1-[2-methylsulphonylaminoethyl]-4-piperidinyl]methyl

1-methyl-1H-indole-3-carboxylate, GR-113808, 3-100 fmol/paw), 5-HT6 (4-iodo-N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]benzene-sulfonamide hydrochloride, SB-258585, 3-10 pmol/paw) and 5-HT7 ((R)-3-(2-(2-(4-methylpiperidin-1-yl) ethyl) pyrrolidine-1-sulfonyl) phenol hydrochloride, SB-269970, 0.3-1 nmol/paw), but not by the 5-HT1A (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-2-pyridinylcyclohexanecarboxamide maleate, WAY-100635, 0.3-1 nmol/paw), 5-HT1B/1D (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2′-methyl-4′-(5-methyl-1,2,4-oxadiazol-3-yl)-1,1′-biphenyl-4-carboxamide www.selleckchem.com/products/loxo-101.html hydrochloride hydrate, GR-127935, 0.3-1 nmol/paw), 5-HT1B (1′-methyl-5-[[2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydrospiro[furo[2,3-f]indole-3,4′-piperidine hydrochloride, SB-224289, 0.3-1 nmol/paw), 5-HT1D (4-(3-chlorophenyl)-alpha-(diphenylmethyl)-1-piperazineethanol

hydrochloride, BRL-15572, 0.3-1 nmol/paw) nor 5-HT5A ((N-[2-(dimethylamino)ethyl]-N-[[4'-[[(2-phenylethyl)amino]methyl] [1,1'-biphenyl]-4-yl]methyl]cyclopentanepropanamide dihydrochloride, SB-699551, 1-3 nmol/paw), receptor antagonists. In marked contrast, the spinal antinociceptive effect of fluoxetine was prevented by the 5-HT1A (WAY-100635, 0.3-1 nmol/rat), Adenosine triphosphate 5-HT1B/1D (DR-127935, 0.3-1 nmol/rat), 5-HT1B (SB-224289, 0.3-1 nmol/rat), 5-HT1D (BRL-15572, 0.3-1 nmol/rat) and 5-HT5A (SB-699551, 1-3 nmol/rat), but not by the 5-HT2A (ketanserin, 3-10 pmol/rat), 5-HT2B (RS-127445, 3-10 pmol/raf), 5-HT2C (RS-102221, 3-10 pmol/rat), 5-HT3 (ondansetron, 3-10 nmol/rat), 5-HT4 (GR-113808, 3-100 fmol/rat), 5-HT6 (SB-258585, 3-10 pmol/rat) nor 5-HT7 (SB-269970, 0.3-1 nmol/rat), receptor antagonists. These results suggest that fluoxetine produces nociception at the periphery by activating peripheral 5-HT2A/2B/2C/3/4/6/7 receptors. In addition, intrathecal fluoxetine produces antinociception by activation of spinal 5-HT1A/1B/1D/5A receptors. (C) 2013 IBRO. Published by Elsevier Ltd.