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Edna Grünblatt, Jasmin Bartl, Susanne Walitza
Methylphenidate (Ritalin) is the most commonly prescribed drug in the treatment of attention-deficit hyperactivity disorder. It is suggested that in vivo, methylphenidate treatment supports cortical maturation, however, the molecular and cellular mechanisms are not well understood. This study aimed to explore the potential effect of methylphenidate on cell proliferation and maturation in various cellular models, hypothesizing its interaction with the Wnt-signaling. The termination of cell proliferation concomitant to neuronal maturation following methylphenidate treatment was observed in all of the cell-models tested: murine neural stem-, rat PC12- and the human SH-SY5Y-cells...
March 1, 2018: Translational Psychiatry
Elvia Mena-Avila, Ricardo Márquez-Gómez, Guillermo Aquino-Miranda, Gustavo Nieto-Alamilla, José-Antonio Arias-Montaño
BACKGROUND: Clobenpropit, a potent antagonist/inverse agonist at the histamine H3 receptor (H3 R), reduced the cytotoxic action of 6-hydroxydopamine (6-OHDA) in neuroblastoma SH-SY5Y cells transfected with the human H3 R. We therefore set out to study whether this effect involved a receptor-independent action on dopamine transport. METHODS: The uptake of [3 H]-dopamine was assayed in SH-SY5Y cells and rat striatal or cerebro-cortical isolated nerve terminals (synaptosomes)...
February 2018: Pharmacological Reports: PR
Anita Cybulska-Klosowicz, Julia Dabrowska, Sebastian Niedzielec, Renata Zakrzewska, Aleksandra Rozycka
Behavioral flexibility is subserved by the prefrontal cortex and the basal ganglia. Orbitofrontal cortex (OFC) and dorsomedial striatum (DMS) form a functional frontocorticostriatal circuit crucial for the mediation of flexibility during reversal learning via dopamine (DA) neurotransmission. The regulatory control in maintaining DA homeostasis and function is provided by the dopamine transporter (DAT), which therefore likely plays a significant role in controlling the influence of DA on cognitive processes...
2017: Acta Neurobiologiae Experimentalis
Mimi Shin, Thomas M Field, Chase S Stucky, Mia N Furgurson, Michael A Johnson
Zebrafish (Danio rerio) have recently emerged as useful model organism for the study of neuronal function. Here, fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes was used to measure locally evoked dopamine release and uptake in zebrafish whole brain preparations and results were compared with those obtained from brain slices. Evoked dopamine release ([DA]max ) was similar in whole brain and sagittal brain slice preparations (0.49 ± 0.13 μM in whole brain and 0.59 ± 0.28 μM in brain slices)...
September 20, 2017: ACS Chemical Neuroscience
L Boekhoudt, T J M Roelofs, J W de Jong, A E de Leeuw, M C M Luijendijk, I G Wolterink-Donselaar, G van der Plasse, R A H Adan
BACKGROUND: Dopamine (DA) signalling in the brain is necessary for feeding behaviour, and alterations in the DA system have been linked to obesity. However, the precise role of DA in the control of food intake remains debated. On the one hand, food reward and motivation are associated with enhanced DA activity. On the other hand, psychostimulant drugs that increase DA signalling suppress food intake. This poses the questions of how endogenous DA neuronal activity regulates feeding, and whether enhancing DA neuronal activity would either promote or reduce food intake...
July 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Maria João Valente, Maria de Lourdes Bastos, Eduarda Fernandes, Félix Carvalho, Paula Guedes de Pinho, Márcia Carvalho
Synthetic cathinones (β-keto amphetamines) act as potent CNS stimulants similarly to classical amphetamines, which raise concerns about their potential neurotoxic effects. The present in vitro study aimed to explore and compare the mechanisms underlying the neurotoxicity of two commonly abused cathinone derivatives, 3,4-methylenedioxymethcathinone (methylone) and 3,4-methylenedioxypyrovalerone (MDPV), with those of 3,4-methylenedioxymethamphetamine (MDMA), using undifferentiated and differentiated SH-SY5Y cells...
April 19, 2017: ACS Chemical Neuroscience
Jonathan M Slezak, Rajeev I Desai, Jonathan L Katz
The present studies compared the acute effects of benztropine analogs (4-Cl-BZT, JHW 007, AHN 1-055), which are atypical dopamine uptake inhibitors, with those of the standard dopamine uptake inhibitors GBR 12909 and cocaine, on the reinforcing efficacy of food and food intake in male Sprague-Dawley rats. Repeated drug effects of JHW 007 on food intake were also determined. The number of ratios completed under a progressive-ratio schedule of food delivery was used as an index of reinforcing efficacy. Food intake was determined by measuring powdered laboratory-chow consumption during daily 40 min food-availability time periods...
February 2017: Behavioural Pharmacology
Vincent D Costa, Laura C Kakalios, Bruno B Averbeck
Dopamine and serotonin have opponent interactions on aspects of impulsivity. Therefore we wanted to test the hypothesis that dopamine and serotonin would have opposing effects on speed-accuracy trade offs in a perceptual decision making task. Unlike other behavioral measures of impulsivity, perceptual decision making allows us to determine whether decreasing premature responses, often interpreted as decreased impulsivity, corresponds to increased behavioral performance. We administered GBR-12909 (a dopamine transporter blocker), escitalopram (a serotonin transporter blocker), or saline in separate sessions to 3 rhesus macaques...
October 2016: Behavioral Neuroscience
Melissa M Conti, Samantha M Meadows, Mitchell Melikhov-Sosin, David Lindenbach, Joy Hallmark, David F Werner, Christopher Bishop
l-DOPA is the standard treatment for Parkinson's disease (PD), but chronic treatment typically leads to abnormal involuntary movement or dyskinesia (LID) development. Although poorly understood, dyskinetic mechanisms involve a complex interaction between the remaining dopamine system and the semi-homologous serotonin and norepinephrine systems. Serotonin and norepinephrine transporters (SERT and NET, respectively) have affinity for dopamine uptake especially when dopamine transporters (DAT) are scant. Monoamine reuptake inhibitors have been reported to modulate l-DOPA's anti-parkinsonian effects, but DAT, SERT, and NET's contribution to dyskinesia has not been well delineated...
November 2016: Neuropharmacology
Antonia Manduca, Michela Servadio, Ruth Damsteegt, Patrizia Campolongo, Louk Jmj Vanderschuren, Viviana Trezza
Social play behavior is a highly rewarding form of social interaction displayed by young mammals. Social play is important for neurobehavioral development and it has been found to be impaired in several developmental psychiatric disorders. In line with the rewarding properties of social play, we have previously identified the nucleus accumbens (NAc) as an important site of action for endocannabinoid and opioid modulation of this behavior. NAc dopamine has a well-known role in certain components of reward processes, such as incentive motivation...
August 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Sarah E Bradshaw, Kara L Agster, Barry D Waterhouse, Jill A McGaughy
Adolescence is a period of major behavioral and brain reorganization. As diagnoses and treatment of disorders like attention deficit hyperactivity disorder (ADHD) often occur during adolescence, it is important to understand how the prefrontal cortices change and how these changes may influence the response to drugs during development. The current study uses an adolescent rat model to study the effect of standard ADHD treatments, atomoxetine and methylphenidate on attentional set shifting and reversal learning...
June 15, 2016: Brain Research
Caleb J Browne, Paul J Fletcher, Fiona D Zeeb
RATIONALE: Environmental factors influence the etiology of many psychiatric disorders. Likewise, environmental factors can alter processes central to motivation. Therefore, motivational deficits present in many disorders may be influenced by early life environmental conditions. OBJECTIVE: We examined whether housing animals in different environmental conditions influenced the ability of sensory stimuli to acquire incentive value and whether elevated monoamine activity altered responsing for these stimuli...
March 2016: Psychopharmacology
Marion France, Emmalee Skorich, Mark Kadrofske, Greg M Swain, James J Galligan
Obesity alters gastrointestinal (GI) motility and 5-HT signalling. Altered 5-HT signalling disrupts control of GI motility. Levels of extracellular 5-HT depend on enterochromaffin (EC) cell release and serotonin transporter (SERT) uptake. We assessed GI transit and 5-HT signalling in the jejunum of normal and obese mice. Male and female mice were fed a control diet (CD; 10% of kilocalories as fat) or a high-fat diet (HFD; 60% of kilocalories as fat). Gastrointestinal transit was increased in male HFD-fed and female CD-fed compared with male CD-fed mice...
January 2016: Experimental Physiology
Amanda J Quisenberry, Lisa E Baker
RATIONALE: Modafinil is a wake-promoting drug with FDA approval for the treatment of excessive daytime sleepiness that has been prescribed for ADHD and recently assessed as a potential treatment for psychostimulant dependence. Previous research indicates that modafinil modestly increases locomotor activity and produces similar discriminative stimulus effects to psychostimulants in rodents, although the subjective effects of modafinil are reportedly distinct from those of cocaine or amphetamine in humans with a history of psychostimulant abuse...
December 2015: Psychopharmacology
Min Sun Choi, Bang-sub Choi, Sang Heon Kim, Sok Cheon Pak, Chul Ho Jang, Young-Won Chin, Young-Mi Kim, Dong-il Kim, Songhee Jeon, Byung-Soo Koo
The dopamine transporter (DAT) protein, a component of the dopamine system, undergoes adaptive neurobiological changes from drug abuse. Prevention of relapse and reduction of withdrawal symptoms are still the major limitations in the current pharmacological treatments of drug addiction. The present study aimed to investigate the effects of essential oils extracted from Elsholtzia ciliata, Shinchim, Angelicae gigantis Radix, and Eugenia caryophyllata, well-known traditional Korean medicines for addiction, on the modulation of dopamine system in amphetamine-treated cells and to explore the possible mechanism underlying its therapeutic effect...
October 2015: Journal of Medicinal Food
E J Marijke Achterberg, Linda W M van Kerkhof, Michela Servadio, Maaike M H van Swieten, Danielle J Houwing, Mandy Aalderink, Nina V Driel, Viviana Trezza, Louk J M J Vanderschuren
Social play behavior, abundant in the young of most mammalian species, is thought to be important for social and cognitive development. Social play is highly rewarding, and as such, the expression of social play depends on its pleasurable and motivational properties. Since the motivational properties of social play have only sporadically been investigated, we developed a setup in which rats responded for social play under a progressive ratio schedule of reinforcement. Dopaminergic neurotransmission plays a key role in incentive motivational processes, and both dopamine and noradrenaline have been implicated in the modulation of social play behavior...
February 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Ana Isabelle G Queiroz, Maíra Moraes de Araújo, Tatiane da Silva Araújo, Greicy Coelho de Souza, Lígia Menezes Cavalcante, Michel de Jesus Souza Machado, David Freitas de Lucena, João Quevedo, Danielle Macêdo
Polymorphisms in the human dopamine transporter (DAT) are associated with bipolar endophenotype. Based on this, the acute inhibition of DAT using GBR12909 causes behavioral alterations that are prevented by valproate (VAL), being related to a mania-like model. Herein our first aim was to analyze behavioral and brain oxidative alterations during a 24 h period post-GBR12909 to better characterize this model. Our second aim was to determine the preventive effects of lithium (Li) or VAL 2 h post-GBR12909. For this, adult male mice received GBR12909 or saline being evaluated at 2, 4, 8, 12 or 24 h post-administration...
October 2015: Metabolic Brain Disease
Andrew M Novick, Gina L Forster, James E Hassell, Daniel R Davies, Jamie L Scholl, Kenneth J Renner, Michael J Watt
Being bullied during adolescence is associated with later mental illnesses characterized by deficits in cognitive tasks mediated by prefrontal cortex (PFC) dopamine (DA). Social defeat of adolescent male rats, as a model of teenage bullying victimization, results in medial PFC (mPFC) dopamine (DA) hypofunction in adulthood that is associated with increased drug seeking and working memory deficits. Increased expression of the DA transporter (DAT) is also seen in the adult infralimbic mPFC following adolescent defeat...
October 2015: Neuropharmacology
Christian Pifl, Harald Reither, Oleh Hornykiewicz
Mephedrone (4-methylmethcathinone, MMC) and 3,4-methylenedioxymethamphetamine (MDMA) are constituents of popular party drugs with psychoactive effects. Structurally they are amphetamine-like substances with monoamine neurotransmitter enhancing actions. We therefore compared their effects on the human monoamine transporters using human cell lines stably expressing the human noradrenaline, dopamine and serotonin transporter (NET, DAT and SERT); preparations of synaptic vesicles from human striatum in uptake experiments; and a superfusion system where releasing effects can be reliably measured...
May 15, 2015: European Journal of Pharmacology
L Barros-Miñones, B Goñi-Allo, V Suquia, G Beitia, N Aguirre, E Puerta
Methylenedioxymethamphetamine (MDMA) causes a persistent loss of dopaminergic cell bodies in the substantia nigra of mice. Current evidence indicates that MDMA-induced neurotoxicity is mediated by oxidative stress probably due to the inhibition of mitochondrial complex I activity. In this study we investigated the contribution of dopamine (DA) to such effects. For this, we modulated the dopaminergic system of mice at the synthesis, uptake or metabolism levels. Striatal mitochondrial complex I activity was decreased 1 h after MDMA; an effect not observed in the striatum of DA depleted mice or in the hippocampus, a dopamine spare region...
June 2015: Neuropharmacology
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