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serotonin and accumbens

Yusuf S Althobaiti, Atiah H Almalki, Sujan C Das, Fahad S Alshehri, Youssef Sari
Repeated exposure to high doses of methamphetamine (METH) is known to alter several neurotransmitters in certain brain regions. Little is known about the effects of ceftriaxone (CEF), a β-lactam antibiotic, known to upregulate glutamate transporter subtype 1, post-treatment on METH-induced depletion of dopamine and serotonin (5-HT) tissue content in brain reward regions. Moreover, the effects of METH and CEF post-treatment on glutamate and glutamine tissue content are not well understood. In this study, Wistar rats were used to investigate the effects of METH and CEF post-treatment on tissue content of dopamine/5-HT and glutamate/glutamine in the nucleus accumbens (NAc) and prefrontal cortex (PFC)...
October 1, 2016: Neuroscience Letters
Eric Murillo-Rodríguez, Khalil Guzmán, Gloria Arankowsky-Sandoval, Mireille Salas-Crisóstomo, Ramsés Jiménez-Moreno, Oscar Arias-Carrión
The peroxisome proliferator-activated receptor alpha (PPARα) is a member of the nuclear receptor superfamily that has been suggested as a modulator of several physiological functions. The PPARα recognizes as an endogenous ligand the anorexic lipid mediator oleoylethanolamide (OEA) which displays wake-inducing properties. Despite that recent evidence indicates that activation of PPARα by synthetic agonists such as Wy14643 enhances waking as well as the extracellular contents of wake-related neurotransmitters, the role of PPARα in sleep recovery after prolonged waking has not been fully described...
September 16, 2016: Brain Research Bulletin
Eoin Sherwin, Valentina Gigliucci, Andrew Harkin
OBJECTIVE: The regional specific modulation of neuronal activation following drug administration is of interest to determine brain areas involved in the behavioural effects of experimental test compounds. In the current investigation the effects of the L-arginine related NOS inhibitor N(ω)-l-nitroarginine (L-NA) and the structurally unrelated selective neuronal NOS inhibitor 1-(2-Trifluoro-methyl-phenyl) imidazole (TRIM) were assessed in the rat for changes in regional c-FOS immunoreactivity, a marker of neuronal activation, upon exposure to the forced swimming test (FST)...
January 1, 2017: Behavioural Brain Research
Ruiyong Wu, Jun Gao, Shinnyi Chou, Collin Davis, Ming Li
As a highly motivated social behavior, maternal behavior in rats has been routinely used to study psychoactive drugs for clinical, neuroscience and pharmacological purposes. Recent evidence indicates that acute activation of serotonin 2C (5-HT2C) receptors causes a disruption of rat maternal behavior. The present study was designed to elucidate the behavioral, pharmacological mechanisms and neuroanatomical basis of this 5-HT2C effect. First, we replicated the finding that acute MK212 injection (2.0mg/kg, a highly selective 5-HT2C agonist) disrupts maternal behavior, especially on pup retrieval...
November 2016: Psychoneuroendocrinology
M F Lazenka, J A Suyama, C T Bauer, M L Banks, S S Negus
3,4-methylenedioxymethamphetamine (MDMA) is a substrate for the dopamine (DA), norepinephrine and serotonin (5HT) transporters that produces greater pharmacological effects on certain endpoints in females than males in both clinical and rodent preclinical studies. To evaluate potential for sex differences in abuse-related MDMA effects, the present study compared MDMA effects on intracranial self-stimulation (ICSS) and on in vivo microdialysis measurements of DA or 5HT in the nucleus accumbens (NAc) in female and male Sprague-Dawley rats...
August 23, 2016: Pharmacology, Biochemistry, and Behavior
Erica Y Shen, Yan Jiang, Behnam Javidfar, Bibi Kassim, Yong-HweeE Loh, Qi Ma, Amanda C Mitchell, Venu Pothula, A Francis Stewart, Patricia Ernst, Wei-Dong Yao, Gilles Martin, Li Shen, Mira Jakovcevski, Schahram Akbarian
Lysine methyltransferase 2a (Kmt2a) and other regulators of H3 lysine 4 methylation, a histone modification enriched at promoters and enhancers, are widely expressed throughout the brain but molecular and cellular phenotypes in subcortical areas remain poorly explored. We report that Kmt2a conditional deletion in postnatal forebrain is associated with excessive nocturnal activity and absent or blunted responses to stimulant and dopaminergic agonist drugs, in conjunction with near-complete loss of spike timing-dependent long term-potentiation (tLTP) in medium spiny neurons...
August 3, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Adem Can, Panos Zanos, Ruin Moaddel, Hye Jin Kang, Katinia S S Dossou, Irving W Wainer, Joseph F Cheer, Douglas O Frost, Xi-Ping Huang, Todd D Gould
Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine's antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine's side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system...
October 2016: Journal of Pharmacology and Experimental Therapeutics
Karolina Noworyta-Sokołowska, Katarzyna Kamińska, Grzegorz Kreiner, Zofia Rogóż, Krystyna Gołembiowska
5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT, 'foxy') is one of the most popular tryptamine hallucinogens in the illicit drug market. It produces serious adverse effects, but its pharmacological profile is not well recognized. In vitro data have shown that 5-MeO-DIPT acts as a potent serotonin transporter (SERT) inhibitor and displays high affinity at serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors. In this study, using microdialysis in freely moving rats, we examined the effect of 5-MeO-DIPT on dopamine (DA), serotonin (5-HT), and glutamate release in the rat striatum, nucleus accumbens, and frontal cortex...
November 2016: Neurotoxicity Research
Jiamei Lian, Bo Pan, Chao Deng
BACKGROUND: Antipsychotic drugs (APDs) were developed to treat schizophrenia in adults; however they have been increasingly prescribed (mostly "off-label") for children and adolescents. This study aimed to investigate the effects of aripiprazole, olanzapine and risperidone on the binding of serotonin (5-HT) and dopamine receptors in juvenile rat brain regions that are involved in antipsychotic efficacy. METHODS: Male and female rats were treated orally with aripiprazole (1mg/kg), olanzapine (1mg/kg), risperidone (0...
October 2016: Pharmacological Reports: PR
Sonya Neto, Ramya Varatharajan, Kevin Joseph, Andreas Moser
Leptin is an anorexigenic hormone that acts via its receptor (LepR) to regulate the hypothalamic arcuate nucleus circuitry to mediate energy homeostasis and feeding behavior. Moreover, leptin decreases the reward value of natural and artificial rewards, and low levels of circulating leptin have been implicated in several mood disorders linking leptin to the mesolimbic system. Therefore, the purpose of this study was to assess whether and to what extent an acute intranasal application of leptin is able to modulate monoamine neurotransmitters in the nucleus accumbens (NAc)...
July 13, 2016: Journal of Neural Transmission
A V Sergutina, V I Rakhmanova
Monoamine oxidase activity was quantitatively assessed by cytochemical method in brain structures (layers III and V of the sensorimotor cortex, caudate nucleus, nucleus accumbens, hippocampal CA3 field) of rats of August line and Wistar population with high and low locomotor activity in the open fi eld test. Monoamine oxidase activity (substrate tryptamine) predominated in the nucleus accumbens of Wistar rats with high motor activity in comparison with rats with low locomotor activity. In August rats, enzyme activity (substrates tryptamine and serotonin) predominated in the hippocampus of animals with high motor activity...
June 2016: Bulletin of Experimental Biology and Medicine
Julia Rummel, Mareike Voget, Ravit Hadar, Samuel Ewing, Reinhard Sohr, Julia Klein, Alexander Sartorius, Andreas Heinz, Aleksander A Mathé, Barbara Vollmayr, Christine Winter
Deep brain stimulation (DBS) of several targets induces beneficial responses in approximately 60% of patients suffering from treatment-resistant depression (TRD). The remaining 40% indicate that these stimulation sites do not bear therapeutic relevance for all TRD patients and consequently DBS-targets should be selected according to individual symptom profiles. We here used two animal models of depression known to have different genetic backgrounds and behavioral responses: the therapy-responsive Flinders sensitive line (FSL) and the therapy-refractory congenitally learned helpless rats (cLH) to study symptom-specific DBS effects i) of different brain sites ii) at different stimulation parameters, and iii) at different expressions of the disease...
October 2016: Journal of Psychiatric Research
Yukio Ago, Shigeru Hasebe, Naoki Hiramatsu, Kazuya Mori, Yuji Watabe, Yusuke Onaka, Hitoshi Hashimoto, Kazuhiro Takuma, Toshio Matsuda
RATIONALE: We previously reported that the fluvoxamine-induced increase in prefrontal dopamine levels is enhanced by adrenalectomy/castration (which results in circulating neurosteroid deficiency), via combined activation of serotonin1A (5-HT1A) and σ1 receptors. However, the mechanistic details of the interaction between 5-HT1A and σ1 receptors are unknown. OBJECTIVES: Because most neurosteroids have affinity for γ-aminobutyric acid (GABA)A receptors, in the present study, we examined the involvement of GABAA receptors in this process...
September 2016: Psychopharmacology
Samantha E Yohn, Emily E Errante, Aaron Rosenbloom-Snow, Matthew Somerville, Margaret Rowland, Kristin Tokarski, Nadia Zafar, Merce Correa, John D Salamone
Deficits in behavioral activation, exertion of effort, and other psychomotor/motivational symptoms are frequently seen in people with depression and other disorders. Depressed people show a decision bias towards selection of low effort activities, and animal tests of effort-related decision making are being used as models of motivational dysfunctions seen in psychopathology. The present studies investigated the ability of drugs that block dopamine transport (DAT), norepinephrine transport (NET), and serotonin transport (SERT) to modulate work output in rats responding on a test of effort-related decision making (i...
October 2016: Neuropharmacology
Robert T Franke, Emilia Tarland, Heidrun Fink, Heinz H Pertz, Jan Brosda
RATIONALE: Recently, we showed that 2-bromoterguride acted as a dopamine D2 receptor partial agonist, a serotonin 5-HT2A and α2C-adrenergic receptor antagonist, and exhibited antidopaminergic efficacy in amphetamine-induced locomotion (AIL) in rats without inducing catalepsy. OBJECTIVE: To extend our knowledge on the antipsychotic effects of 2-bromoterguride, we used convergent preclinical animal models and tests; i.e., conditioned avoidance response (CAR), predictive of antipsychotic-like effects; Fos protein expression, a molecular marker for (atypical) antipsychotic activity; wet dog shake behavior, a test for the in vivo effects of drugs acting on central 5-HT2A receptors; and investigated metabolic changes as a common side effect of atypical antipsychotic drugs (APDs)...
August 2016: Psychopharmacology
Noemí Santana, Francesc Artigas
The prefrontal cortex (PFC) is enriched in several serotonin receptors, including 5-HT1A-R, 5-HT2A-R, and 5-HT3-R. These receptors modulate PFC activity due to their expression in large neuronal populations (5-HT1A-R, 5-HT2A-R) or in selected GABAergic populations (5-HT3-R). They are also relevant for antidepressant and antipsychotic drug action. Less is known about the localization of 5-HT2C-R, for which atypical antipsychotics show high affinity. Here, we report on the cellular distribution of 5-HT2C-R in rat PFC and striatum, using double in situ hybridization histochemistry...
June 1, 2016: Cerebral Cortex
J M Witkin, J A Monn, D D Schoepp, X Li, C Overshiner, S N Mitchell, G Carter, B Johnson, K Rasmussen, L M Rorick-Kehn
Ketamine is a rapidly acting antidepressant in patients with treatment-resistant depression (TRD). Although the mechanisms underlying these effects are not fully established, inquiry to date has focused on the triggering of synaptogenesis transduction pathways via glutamatergic mechanisms. Preclinical data suggest that blockade of metabotropic glutamate (mGlu2/3) receptors shares many overlapping features and mechanisms with ketamine and may also provide rapid efficacy for TRD patients. Central dopamine circuitry is recognized as an end target for mood regulation and hedonic valuation and yet has been largely neglected in mechanistic studies of antidepressant-relevant effects of ketamine...
July 2016: Journal of Pharmacology and Experimental Therapeutics
Minjeong Kim, Jin-Gyeom Lee, Chae Ha Yang, Sooyeun Lee
Accurate measurement of trace levels of endogenous compounds remains challenging despite advancements in analytical technologies. In particular, monoamine neurotransmitters such as dopamine (DA) and serotonin (5-HT) are polar compounds with low molecular weights, which complicates the optimization of retention and detection on liquid chromatography-mass spectrometry (LC-MS). Microdialysis is an important sampling technique to collect extracellular fluid from the brain of living animals. However, the very low basal concentrations of the neurotransmitters, small sample volume (maximum 30 μL) and the absence of matrix-matching calibrators are limitations of a microdialysate as an analytical sample...
June 7, 2016: Analytica Chimica Acta
Philipp Hinderberger, Michael Rullmann, Mandy Drabe, Julia Luthardt, Georg-Alexander Becker, Matthias Blüher, Ralf Regenthal, Osama Sabri, Swen Hesse
BACKGROUND: Serotonin (5-HT) and its neurotrophic support system, specifically brain-derived neurotrophic factor (BDNF), are thought to modulate energy homeostasis and susceptibility to obesity. Moreover, a polymorphism (5-HTTLPR) in the serotonin reuptake transporter (5-HTT) gene impairs its transcription, thereby altering serotonergic tone and potentially contributing to such susceptibility. This study aims to investigate the effect of BDNF, biallelic 5-HTTLPR, and central in-vivo 5-HTT availability in highly obese versus non-obese subjects using positron emission tomography (PET) and 5-HTT selective [(11)C]DASB...
November 2016: Neuropharmacology
Magdalena Jastrzębska-Więsek, Agata Siwek, Anna Partyka, Lucyna Antkiewicz-Michaluk, Jerzy Michaluk, Irena Romańska, Marcin Kołaczkowski, Anna Wesołowska
It was shown that 5-HT6 receptor agonists can exert pharmacological activity due to various modifications in monoamines' level and metabolism activity in rats' brain structures. This finding was correlated with antidepressant- or anxiolytic-like properties of these compounds. The study was designed to establish a possible mechanism of the antidepressant-like activity of the partial 5-HT6 receptor agonist EMD386088 (5-chloro-2-methyl-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-indole hydrochloride) in rats. The concentrations of monoamines (dopamine (DA), noradrenaline (NA), and serotonin (5-HT)) and the rate of their metabolism were measured ex vivo in the brain structures (hippocampus, nucleus accumbens, striatum) using high-performance liquid chromatography (HPLC)...
August 2016: Naunyn-Schmiedeberg's Archives of Pharmacology
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