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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
Maarten E A Reith, Bruce E Blough, Weimin C Hong, Kymry T Jones, Kyle C Schmitt, Michael H Baumann, John S Partilla, Richard B Rothman, Jonathan L Katz
BACKGROUND: Treatment of stimulant-use disorders remains a formidable challenge, and the dopamine transporter (DAT) remains a potential target for antagonist or agonist-like substitution therapies. METHODS: This review focuses on DAT ligands, such as benztropine, GBR 12909, modafinil, and DAT substrates derived from phenethylamine or cathinone that have atypical DAT-inhibitor effects, either in vitro or in vivo. The compounds are described from a molecular mechanistic, behavioral, and medicinal-chemical perspective...
February 1, 2015: Drug and Alcohol Dependence
M Squillace, L Dodero, M Federici, S Migliarini, F Errico, F Napolitano, P Krashia, A Di Maio, A Galbusera, A Bifone, M L Scattoni, M Pasqualetti, N B Mercuri, A Usiello, A Gozzi
Autism spectrum disorders (ASD) are neurodevelopmental conditions characterized by pronounced social and communication deficits and stereotyped behaviours. Recent psychosocial and neuroimaging studies have highlighted reward-processing deficits and reduced dopamine (DA) mesolimbic circuit reactivity in ASD patients. However, the neurobiological and molecular determinants of these deficits remain undetermined. Mouse models recapitulating ASD-like phenotypes could help generate hypotheses about the origin and neurophysiological underpinnings of clinically relevant traits...
2014: Translational Psychiatry
Christopher W Atcherley, Nicholas D Laude, Eric B Monroe, Kevin M Wood, Parastoo Hashemi, Michael L Heien
The distribution and density of neurons within the brain poses many challenges when making quantitative measurements of neurotransmission in the extracellular space. A volume neurotransmitter is released into the synapse during chemical communication and must diffuse through the extracellular space to an implanted sensor for real-time in situ detection. Fast-scan cyclic voltammetry is an excellent technique for measuring biologically relevant concentration changes in vivo; however, the sensitivity is limited by mass-transport-limited adsorption...
September 16, 2015: ACS Chemical Neuroscience
Felice Iasevoli, Elisabetta F Buonaguro, Chiara Sarappa, Federica Marmo, Gianmarco Latte, Rodolfo Rossi, Anna Eramo, Carmine Tomasetti, Andrea de Bartolomeis
A relevant role for dopamine-glutamate interaction has been reported in the pathophysiology and treatment of psychoses. Dopamine and glutamate may interact at multiple levels, including the glutamatergic postsynaptic density (PSD), an electron-dense thickening that has gained recent attention as a switchboard of dopamine-glutamate interactions and for its role in synaptic plasticity. Recently, glutamate-based strategies, such as memantine add-on to antipsychotics, have been proposed for refractory symptoms of schizophrenia, e...
October 3, 2014: Progress in Neuro-psychopharmacology & Biological Psychiatry
Susan Smittkamp, Heather Spalding, Hongyu Zhang, John A Stanford
RATIONALE: Orolingual motor deficits, such as dysarthria and dysphagia, contribute to increased morbidity and mortality in the elderly. In preclinical studies, we and others have reported age-related decreases in tongue motility in both F344 and F344/BN rats. The fact that these deficits are associated with nigrostriatal dopamine (DA), tissue measures suggest that increasing dopamine function might normalize tongue motility. OBJECTIVE: The purpose of the current study was to determine whether two indirect dopamine agonists with locomotor-enhancing effects, d-amphetamine (amphetamine; 1 and 2 mg/kg) and GBR-12909 (5, 10, and 20 mg/kg), can improve tongue motility in aged F344/BN rats...
December 2014: Psychopharmacology
Vincent D Costa, Valery L Tran, Janita Turchi, Bruno B Averbeck
Novelty seeking refers to the tendency of humans and animals to explore novel and unfamiliar stimuli and environments. The idea that dopamine modulates novelty seeking is supported by evidence that novel stimuli excite dopamine neurons and activate brain regions receiving dopaminergic input. In addition, dopamine is shown to drive exploratory behavior in novel environments. It is not clear whether dopamine promotes novelty seeking when it is framed as the decision to explore novel options versus the exploitation of familiar options...
October 2014: Behavioral Neuroscience
Meng Sun, Sam V Kaplan, Rachel C Gehringer, Ryan A Limbocker, Michael A Johnson
The use of fast scan cyclic voltammetry (FSCV) to measure the release and uptake of dopamine (DA) as well as other biogenic molecules in viable brain tissue slices has gained popularity over the last 2 decades. Brain slices have the advantage of maintaining the functional three-dimensional architecture of the neuronal network while also allowing researchers to obtain multiple sets of measurements from a single animal. In this work, we describe a simple, easy-to-fabricate perfusion device designed to focally deliver pharmacological agents to brain slices...
May 6, 2014: Analytical Chemistry
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