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Dionisio A Amodeo, Elaine Rivera, Edwin H Cook, John A Sweeney, Michael E Ragozzino
Restricted and repetitive behaviors are a defining feature of autism which can be expressed as a cognitive flexibility deficit or stereotyped, motor behaviors. There is limited knowledge about the underlying neuropathophysiology contributing to these behaviors. Previous findings suggest that central 5HT2A receptor activity is altered in autism, while recent work indicates that systemic 5HT2A receptor antagonist treatment reduces repetitive behaviors in an idiopathic model of autism. 5HT2A receptors are expressed in the orbitofrontal cortex and striatum...
September 22, 2016: Genes, Brain, and Behavior
Thi Thu Ha Nguyen, Antoine Pariente, Jean-Louis Montastruc, Maryse Lapeyre-Mestre, Vanessa Rousseau, Olivier Rascol, Bernard Bégaud, François Montastruc
AIMS: Pharmacovigilance databases are usually used to detect new potential signals relevant for drug safety. They are seldom used for explanatory purposes, e.g. to understand the mechanisms of adverse drug reactions (ADRs). The aim of the present study was to combine pharmacovigilance and pharmacodynamic data to investigate the association between D2, 5HT2A, and M1 receptor occupancy and the risks of antipsychotic (AP)-induced movement disorders. METHODS: First, we performed a case non-case analysis using spontaneous reports from the World Health Organization (WHO) Global Individual Case Safety Report (ICSR) database, VigiBase®...
September 30, 2016: British Journal of Clinical Pharmacology
James L Klotz, Glen E Aiken, Jessica R Bussard, Andrew P Foote, David L Harmon, Ben M Goff, F Neal Schrick, James R Strickland
Previous research has indicated that serotonergic and α-adrenergic receptors in peripheral vasculature are affected by exposure of cattle grazing toxic endophyte-infected (E+; Epichlöe coenophialia) tall fescue (Lolium arundinaceum). The objective of this experiment was to determine the period of time necessary for the vascular effects of ergot alkaloids to subside. Two experiments were conducted to investigate changes in vascular contractile response and vasoconstriction over time relative to removal from an ergot alkaloid-containing E+ tall fescue pasture...
2016: Toxins
Satoshi Shimegi, Akihiro Kimura, Akinori Sato, Chisa Aoyama, Ryo Mizuyama, Keisuke Tsunoda, Fuyuki Ueda, Sera Araki, Ryoma Goya, Hiromichi Sato
The brain dynamically changes its input-output relationship depending on the behavioral state and context in order to optimize information processing. At the molecular level, cholinergic/monoaminergic transmitters have been extensively studied as key players for the state/context-dependent modulation of brain function. In this paper, we review how cortical visual information processing in the primary visual cortex (V1) of macaque monkey, which has a highly differentiated laminar structure, is optimized by serotonergic and cholinergic systems by examining anatomical and in vivo electrophysiological aspects to highlight their similarities and distinctions...
September 9, 2016: Journal of Physiology, Paris
Jennifer Ro, Gloria Pak, Paige A Malec, Yang Lyu, David B Allison, Robert T Kennedy, Scott D Pletcher
Research into how protein restriction improves organismal health and lengthens lifespan has largely focused on cell-autonomous processes. In certain instances, however, nutrient effects on lifespan are independent of consumption, leading us to test the hypothesis that central, cell non-autonomous processes are important protein restriction regulators. We characterized a transient feeding preference for dietary protein after modest starvation in the fruit fly, Drosophila melanogaster, and identified tryptophan hydroxylase (Trh), serotonin receptor 2a (5HT2a), and the solute carrier 7-family amino acid transporter, JhI-21, as required for this preference through their role in establishing protein value...
2016: ELife
Isabella Salzer, Enkhbileg Gantumur, Arsalan Yousuf, Stefan Boehm
Serotonin (5HT) is a constituent of the so-called "inflammatory soup" that sensitizes nociceptors during inflammation. Nevertheless, receptors and signaling mechanisms that mediate an excitation of dorsal root ganglion (DRG) neurons by 5HT remained controversial. Therefore, capsaicin-sensitive nociceptive neurons dissociated from rat DRGs were used to investigate effects of 5HT on membrane excitability and currents through ligand- as well as voltage-gated ion channels. In 58% of the neurons tested, 5HT increased action potential firing, an effect that was abolished by the 5HT2 receptor antagonist ritanserin, but not by the 5HT3 antagonist tropisetron...
November 2016: Neuropharmacology
Stephen M Stahl
Pimavanserin, a novel agent approved for the treatment of Parkinson's disease psychosis, has potent actions as an antagonist/inverse agonist at serotonin 5HT2A receptors and less potent antagonist/inverse agonist actions at 5HT2C receptors.
August 2016: CNS Spectrums
Joanna Pawlak, Monika Dmitrzak-Weglarz, Monika Wilkosc, Aleksandra Szczepankiewicz, Anna Leszczynska-Rodziewicz, Dorota Zaremba, Pawel Kapelski, Aleksandra Rajewska-Rager, Joanna Hauser
INTRODUCTION: Studies have not given yet a clear answer what is the genetic background of suicidal predisposition. The associations between polymorphisms of the TPH1 and 5-HTTLPR genes and violent suicidal behavior was revealed with the least inconsistencies. METHOD: We selected 10 "strong candidate genes" and 35 SNPs, SLC6A4 and ACP1 for replication study. We searched associations between precisely described suicidal phenotype in 825 affective patients and polymorphisms of selected neurobiological pathways genes as well as their interactions that constitute suicidal risk...
July 19, 2016: Journal of Affective Disorders
Dionisio A Amodeo, Elaine Rivera, Jeffrey T Dunn, Michael E Ragozzino
Individuals with autism spectrum disorder (ASD) exhibit social-communication deficits along with restricted interests and repetitive behaviors (RRBs). To date, there is a lack of effective treatments to alleviate RRBs. A recent study found that treatment with the 5HT2A receptor antagonist M100907 attenuates a reversal learning deficit in the BTBR mouse model of autism. The BTBR mouse also exhibits elevated grooming behavior which may model stereotyped motor behaviors also observed in ASD. The present study examined whether 5HT2A receptor blockade with M100907 at either 0...
October 15, 2016: Behavioural Brain Research
Robert H Howland
Antidepressant, atypical antipsychotic, and hallucinogen drugs mediate their actions in part by interactions with the serotonin-2A (5HT2A) receptor. Serotonergic hallucinogen drugs, such as psilocybin, bind most potently as agonists at the 5HT2A receptor, producing profound changes in perception, mood, and cognition. Some of these drugs have been or are currently being investigated in small Phase 2 studies for depression, alcoholism, smoking cessation, anxiety, and posttraumatic stress disorder. However, unlike the synergistic effects of combining antidepressant and atypical antipsychotic drugs, the potential therapeutic effects of hallucinogen drugs may be attenuated by the concurrent use of these medications because antidepressant and atypical antipsychotic drugs desensitize and/or down-regulate 5HT2A receptors...
July 1, 2016: Journal of Psychosocial Nursing and Mental Health Services
Dawn Bruijnzeel, Rajiv Tandon
Antipsychotic agents, utilized for the treatment of a range of psychiatric disorders, differ substantially in terms of their pharmacology and adverse effect profiles. Incomplete and variable efficacy, differences in safety-tolerability, and highly heterogeneous response across individuals prompt development of new agents. Brexpiprazole is one of the two most recently introduced antipsychotic agents approved for the treatment of schizophrenia and as an adjunct for treatment of major depressive disorder. Its pharmacology, clinical trial data, and efficacy and side effects in comparison with other antipsychotic agents are discussed...
2016: Drug Design, Development and Therapy
Robert H Howland
Approximately all clinically useful antipsychotic drugs have known activity as dopamine receptor antagonists, but many of these drugs also are inverse agonists at the serotonin-2A (5HT2A) receptor. Pimavanserin is an inverse agonist at the 5HT2A receptor, with a lower binding affinity at the serotonin-2C receptor and sigma 1 receptor, but no significant binding to dopamine or other receptors. Because of its unique pharmacology, pimavanserin was approved for the treatment of psychosis associated with Parkinson's disease, and it has a low risk for exacerbating motor symptoms compared to standard antipsychotic medications...
June 1, 2016: Journal of Psychosocial Nursing and Mental Health Services
Donatella Marazziti, Armando Piccinni, Stefano Baroni, Francesco Mungai, Silvio Presta, Federico Mucci, Liliana Dell'Osso
Over the years, both first- (FGAs) and second-generation antipsychotics (SGAs), continue to gain increasing evidence of being effective in the treatment of psychotic symptoms. Currently, they represent the first-line treatment of schizophrenia and bipolar disorder, although they are widely used in psychotic depression and other clinical conditions, such as agitation and/or behavioural disturbances. Despite representing an indispensable tool for the treatment of severe psychotic disorders, they are widely known to have a number of unwanted side effects that the clinician must be aware of, and handle carefully to provide the patient the best available treatment in the short and long-term...
2016: Current Medicinal Chemistry
Aung Aung Kywe Moe, Nyoman D Kurniawan, Suzanne Alexander, Xiaoying Cui, Thomas H J Burne, Darryl W Eyles
Adolescence is a period of dynamic remodeling and maturation in the brain. Exposure to psychotropic drugs during adolescence can potentially alter neural maturation in the adolescent brain subsequently altering neural function at maturity. In this regard, antipsychotic drugs (APDs) are important given a notable global increase in prescription of these APDs to adolescents for a variety of behavioural symptoms and conditions over the past twenty years. However, there is a paucity of data on the long-term consequences of APDs on the adolescent brain...
September 2016: Neuropharmacology
Amanda M K Madden, Alexandria T Paul, Rory A Pritchard, Rebecca Michel, Susan L Zup
Testosterone and its metabolites masculinize the brain during a critical perinatal window, including the relative volume of sexually dimorphic brain areas such as the sexually dimorphic nucleus of the preoptic area (SDN), which is larger in males than females. Serotonin (5HT) may mediate this hormone action, since 5HT given during the second week of life decreases (i.e., feminizes) SDN volume in males and testosterone-treated females. Although previous work indicates that the 5HT2A/2C receptor is sufficient to induce feminization, it is unclear whether other serotonin receptors are required and which subpopulation(s) of SDN cells are specifically organized by 5HT...
February 22, 2016: Developmental Neurobiology
Alice Trentalange, Andrea Calcagno, Valeria Ghisetti, Cristiana Atzori, Paolo Busolli, Stefano Bonora, Daniele Imperiale
Progressive multifocal leukoencephalopathy (PML) is a severe encephalic demyelinating disease associated with JC virus (JCV) reactivation that occurs mostly in patients with immune disorders. Patients affected by sarcoidosis are at risk for developing PML both for leukocyte dysfunction and for receiving immunosuppressive medications: delayed diagnosis and high-dose corticosteroids are associated with a reduced survival. Although no specific treatment for PML exists, several therapeutic possibilities have been assessed with uncertain benefits (5HT2a receptor inhibitors are active in vitro against JCV): the cornerstone of sarcoidosis-associated PML is immunosuppressants withdrawal...
February 9, 2016: Antiviral Therapy
Carl Alexander Roberts, Andrew Jones, Catharine Montgomery
We conducted a meta-analysis on the available data from studies investigating SERTs in ecstasy users and polydrug using controls. From 7 studies we compared data from 157 ecstasy users and 148 controls across 14 brain regions. The main effect suggested ecstasy/MDMA related SERT reductions (SMD=0.52, 95% CIs [0.40, 0.65]; Z=8.36, p<.01, I(2)=89%). A significant effect of subgroups (X(2)=37.41, df=13, p<.01, I(2)=65.3%) suggested differential effects across brain ROIs. Ecstasy users showed significant SERT reductions in 11 out of the 14 regions, including every neocortical and limbic region analysed...
April 2016: Neuroscience and Biobehavioral Reviews
Carla García-Barba, Laura Medina-Ceja
Fast ripples (FR, 250-600Hz) are field potentials that occur only in those areas capable of generating seizures, such as the hippocampus, and modulation of FR by serotonin has been reported. Therefore, we hypothesized that the receptor antagonists 5HT1A and 5HT2A, B, C will increase FR in rats treated with kainic acid (KA, 0.8μg/0.5μl). For this purpose, the intracranial EEG recordings of the hippocampus from animals treated with KA and the serotonin antagonists WAY100135 and ritanserin (dose 0.2mg/Kg, i...
March 2016: Brain Research Bulletin
Kornél Demeter, Bibiána Török, Anna Fodor, János Varga, Szilamér Ferenczi, Krisztina J Kovács, Ildikó Eszik, Viktor Szegedi, Dóra Zelena
Schizophrenia-like symptoms were detected in vasopressin-deficient (di/di) Brattleboro rats, and it was also suggested that schizophrenia might have an epigenetic component. We aimed to clarify if epigenetic changes contribute to schizophrenia-like behavior of this strain. Behavioral (locomotion by telemetry, cognition by novel object recognition, social recognition and social avoidance test, attention by pre-pulse inhibition) and epigenetic differences were compared between wild type and di/di animals. DNA methyltransferase1 (DNMT1), DNMT3a, as well as COMT, GAD, VGLUT1, 5HT2A, BDNF mRNA levels in prefrontal brain region and hippocampus were studied by qRT-PCR...
March 1, 2016: Behavioural Brain Research
Stuart A Collins, Courtney Huff, Nicolas Chiaia, Gary A Gudelsky, Bryan K Yamamoto
3,4-methylenedioxymethamphetamine (MDMA) is a widely abused psychostimulant, which causes release of serotonin in various forebrain regions. Recently, we reported that MDMA increases extracellular glutamate concentrations in the dentate gyrus, via activation of 5HT2A receptors. We examined the role of prostaglandin signaling in mediating the effects of 5HT2A receptor activation on the increases in extracellular glutamate and the subsequent long-term loss of parvalbumin interneurons in the dentate gyrus caused by MDMA...
March 2016: Journal of Neurochemistry
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