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Dopamine reuptake

Laurence D Picton, Keith T Sillar
Dopamine plays important roles in the development and modulation of motor control circuits. Here we show that dopamine exerts potent effects on the central pattern generator circuit controlling locomotory swimming in post-embryonic Xenopus tadpoles. Dopamine (0.5-100 μM) reduced fictive swim bout occurrence and caused both spontaneous and evoked episodes to become shorter, slower and weaker. The D2-like receptor agonist quinpirole mimicked this repertoire of inhibitory effects on swimming, whilst the D4 receptor antagonist, L745,870, had the opposite effects...
October 20, 2016: Scientific Reports
Mark J Millan, Jean-Michel Rivet, Alain Gobert
The highly-interconnected and neurochemically-rich frontal cortex plays a crucial role in the regulation of mood and cognition, domains disrupted in depression and other central nervous system disorders, and it is an important site of action for their therapeutic control. For improving our understanding of the function and dysfunction of the frontal cortex, and for identifying improved treatments, quantification of extracellular pools of neuromodulators by microdialysis in freely-moving rodents has proven indispensable...
October 17, 2016: Journal of Psychopharmacology
Katarzyna Kamińska, Karolina Noworyta-Sokołowska, Alexandra Jurczak, Anna Górska, Zofia Rogóż, Krystyna Gołembiowska
BACKGROUND: Schizophrenia is a psychiatric disorder characterized by positive and negative symptoms often accompanied by depression and cognitive deficits. Positive symptoms, like delusions and hallucinations are caused by an excess of dopamine (DA) signaling and are treated with the second generation antipsychotic drugs. Negative symptoms of schizophrenia are represented by social withdrawal, apathy and blunted emotional response. It was demonstrated that co-administration of risperidone and selective serotonin reuptake inhibitors alleviated depressive symptoms and cognitive dysfunction in animal models of schizophrenia...
September 11, 2016: Pharmacological Reports: PR
Michael P Saddoris
Repeated self-administration of cocaine is associated with impairments in motivated behaviors as well as alterations in both dopamine (DA) release and neural signaling within the nucleus accumbens (NAc). These impairments are present even after several weeks of abstinence from drug taking, suggesting that the self-administration experience induces long-lasting neuroplastic alterations in the mesolimbic DA circuit. To understand these changes at the terminal level, rats were allowed to self-administer either cocaine intravenously (∼1 mg/kg per infusion) or water to a receptacle (control) in 2-h sessions over 14 days, followed by 30 days of enforced abstinence...
September 2016: ENeuro
Lei-Fang Cao, Xiao-Yan Peng, Ya Huang, Bing Wang, Feng-Ming Zhou, Ruo-Xiao Cheng, Li-Hua Chen, Wei-Feng Luo, Tong Liu
In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats...
2016: Neural Plasticity
P Cordery, N Peirce, R J Maughan, P Watson
Catecholamine reuptake inhibition improves the performance of male volunteers exercising in warm conditions, but sex differences in thermoregulation, circulating hormones, and central neurotransmission may alter this response. With local ethics committee approval, nine physically active women (mean ± SD age 21 ± 2 years; height 1.68 ± 0.08 m; body mass 64.1 ± 6.0 kg; VO2peak 51 ± 7 mL/kg/min) were recruited to examine the effect of pre-exercise administration of Bupropion (BUP; 4 × 150 mg) on prolonged exercise performance in a warm environment...
October 13, 2016: Scandinavian Journal of Medicine & Science in Sports
Patricia Pilkinton, Carlos Berry, Seth Norrholm, Al Bartolucci, Badari Birur, Lori L Davis
OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) remain the first-line treatment for posttraumatic stress disorder (PTSD). However, adjunctive atypical antipsychotics are often used to target residual or refractory symptoms. Asenapine is a novel atypical antipsychotic that possesses a high serotonin (5-HT2A) to dopamine (D2) affinity ratio and alpha-adrenergic antagonism, which may be advantageous in treating PTSD. This pilot study aimed to identify the therapeutic potential of asenapine as an adjunctive treatment for PTSD...
August 15, 2016: Psychopharmacology Bulletin
Jadwiga Nędza, Renata Polaniak, Rafał J Bułdak, Milena Majchrzak, Joanna Margasiń-Ska, Marcin Rojkiewicz, Rafał Celiński, Elżbieta Grochowska-Niedworok
Recently, there has been an increase in the consumption of designer drugs, substances aimed at producing psychoactive, energizing, euphoric or anesthetic effects. Designer drugs are substitutes of actual narcotics, whose possession is banned under Polish law according to the Act of 29 July 2005. The latest reports suggest that the number of synthetic psychoactive substances is increasing. In the span of 2012, a total of 28 new synthetic cannabinoids were discovered in member states of the European Union. Synthetic psychoactive substances appear in different forms on the market: tablets (often very colourful and interestingly-shaped), seeds, dried product (sprayed with synthetic substance and redried), crystals or powder...
July 29, 2016: Polski Merkuriusz Lekarski: Organ Polskiego Towarzystwa Lekarskiego
Yoon Sun Cho, Chih-Na Yen, Joong Sup Shim, Dong Hoon Kang, Sang Won Kang, Jun O Liu, Ho Jeong Kwon
Indatraline is an antidepressive agent and a non-selective monoamine transporter inhibitor that blocks the reuptake of neurotransmitters (dopamine, serotonin, and norepinephrine). In this study, we report that indatraline induces autophagy via the suppression of mTOR/S6 kinase signaling. Autophagy induction was examined by a cell-based high content screening system using LysoTracker, which was followed by monodansylcadaverine staining and transmission electron microscope observation. Indatraline increased the number of EGFP-LC3 cells expressing autophagosomes in the cytoplasm...
October 3, 2016: Scientific Reports
Wanhong Zuo, Liwei Wang, Lixin Chen, Krešimir Krnjević, Rao Fu, Xia Feng, Wen He, Seungwoo Kang, Avi Shah, Alex Bekker, Jiang-Hong Ye
Ethanol's aversive property may limit it's use, but the underlying mechanisms are no well-understood. Emerging evidence suggests a critical role for the lateral habenula (LHb) in the aversive response to various drugs, including ethanol. We previously showed that ethanol enhances glutamatergic transmission and stimulates LHb neurons. GABAergic transmission, a major target of ethanol in many brain regions, also tightly regulates LHb activity. This study assessed the action of ethanol on LHb GABAergic transmission in rat brain slices...
September 25, 2016: Neuropharmacology
Akash Pandhare, Aneesh Satya Pappu, Henrik Wilms, Michael Paul Blanton, Michaela Jansen
The FDA-approved antidepressant and smoking cessation drug bupropion is known to inhibit dopamine and norepinephrine reuptake transporters, as well as nicotinic acetylcholine receptors (nAChRs) which are cation-conducting members of the Cys-loop superfamily of ion channels, and more broadly pentameric ligand-gated ion channels (pLGICs). In the present study, we examined the ability of bupropion and its primary metabolite hydroxybupropion to block the function of cation-selective serotonin type 3A receptors (5-HT3ARs), and further characterized bupropion's pharmacological effects at these receptors...
September 24, 2016: Neuropharmacology
Chris G McMahon
Over the past 20-30 years, the premature ejaculation (PE) treatment paradigm, previously limited to behavioural psychotherapy, has expanded to include drug treatment. Pharmacotherapy for PE predominantly targets the multiple neurotransmitters and receptors involved in the control of ejaculation which include serotonin, dopamine, oxytocin, norepinephrine, gamma amino-butyric acid (GABA) and nitric oxide (NO). The objective of this article is to review emerging PE interventions contemporary data on the treatment of PE was reviewed and critiqued using the principles of evidence-based medicine...
August 2016: Translational Andrology and Urology
Suresh Paudel, Srijan Acharya, Goo Yoon, Kyeong-Man Kim, Seung Hoon Cheon
In the search for potent dual norepinephrine and dopamine reuptake inhibitors, several substituted arylpiperazine-tetrazoles were designed, synthesized and evaluated for their neurotransmitter reuptake inhibitory activities. Various derivatives exhibited selective and strong neurotransmitter reuptake inhibitory activity. In particular, compounds with a three-carbon linker displayed selective and stronger potency than those with two-carbon and four-carbon linkers. Interestingly, six compounds, 9b, 9c, 9d, 9o, 9q and 9u displayed more effective activity than the standard drug, bupropion...
November 1, 2016: Bioorganic & Medicinal Chemistry
Natalie R Sealover, Bruce Felts, Charles P Kuntz, Rachel E Jarrard, Gregory H Hockerman, Eric L Barker, L Keith Henry
The substituted amphetamine, 3,4-methylenedioxy-methamphetamine (MDMA, ecstasy), is a widely used drug of abuse that induces non-exocytotic release of serotonin, dopamine, and norepinephrine through their cognate transporters as well as blocking the reuptake of neurotransmitter by the same transporters. The resulting dramatic increase in volume transmission and signal duration of neurotransmitters leads to psychotropic, stimulant, and entactogenic effects. The mechanism by which amphetamines drive reverse transport of the monoamines remains largely enigmatic, however, promising outcomes for the therapeutic utility of MDMA for post-traumatic stress disorder and the long-time use of the dopaminergic and noradrenergic-directed amphetamines in treatment of attention-deficit hyperactivity disorder and narcolepsy increases the importance of understanding this phenomenon...
September 13, 2016: Biochemical Pharmacology
Q S Li, C Tian, G R Seabrook, W C Drevets, V A Narayan
Genetic predisposition may contribute to the differences in drug-specific, class-specific or antidepressant-wide treatment resistance. Clinical studies with the genetic data are often limited in sample sizes. Drug response obtained from self-reports may offer an alternative approach to conduct a study with much larger sample size. Using the phenotype data collected from 23andMe 'Antidepressant Efficacy and Side Effects' survey and genotype data from 23andMe's research participants, we conducted genome-wide association study (GWAS) on subjects of European ancestry using four groups of phenotypes (a) non-treatment-resistant depression (n=7795) vs treatment-resistant depression (TRD, n=1311), (b) selective serotonin reuptake inhibitors (SSRI) responders (n=6348) vs non-responders (n=3340), (c) citalopram/escitalopram responders (n=2963) vs non-responders (n=2005), and (d) norepinephrine-dopamine reuptake inhibitor (NDRI, bupropion) responders (n=2675) vs non-responders (n=1861)...
2016: Translational Psychiatry
Daniel P Bermingham, Randy D Blakely
Modulation of neurotransmission by the monoamines dopamine (DA), norepinephrine (NE), and serotonin (5-HT) is critical for normal nervous system function. Precise temporal and spatial control of this signaling in mediated in large part by the actions of monoamine transporters (DAT, NET, and SERT, respectively). These transporters act to recapture their respective neurotransmitters after release, and disruption of clearance and reuptake has significant effects on physiology and behavior and has been linked to a number of neuropsychiatric disorders...
October 2016: Pharmacological Reviews
Jeffery N Talbot, Laura M Geffert, Jessica E Jorvig, Ruben I Goldstein, Cienna L Nielsen, Nicholas E Wolters, Mary Ellen Amos, Caitlin A Munro, Elizabeth Dallman, Maddalena Mereu, Gianluigi Tanda, Jonathan L Katz, Martín Indarte, Jeffry D Madura, Hailey Choi, Rehana K Leak, Christopher K Surratt
Rational design of lead compounds targeting monoamine transporters (MATs) is critical to developing novel therapeutics to treat psychiatric disorders including depression and substance abuse. A 3-D dopamine transporter (DAT) computer model was used to virtually screen a commercially available small molecule library for high DAT affinity drug-like compounds. One hit, coded "MI-4", inhibited human dopamine, norepinephrine, and serotonin transporters in vitro. In vivo administration in mice induced robust, dose-dependent antidepressant-like behaviors in learned helplessness models (tail suspension and forced swim tests)...
August 26, 2016: Pharmacology, Biochemistry, and Behavior
Maddalena Mereu, Lauren E Chun, Thomas Prisinzano, Amy Hauck Newman, Jonathan L Katz, Gianluigi Tanda
Blockade of dopamine (DA) reuptake via the dopamine transporter (DAT) is a primary mechanism identified as underlying the therapeutic actions of (±)-modafinil (modafinil) and its R-enantiomer, armodafinil. Herein, we explored the neurochemical and behavioral actions of modafinil to better characterize its psychostimulant profile. Swiss-Webster mice were implanted with microdialysis probes in the nucleus accumbens shell (NAS) or core (NAC) to evaluate changes in DA levels related to acute reinforcing actions of drugs of abuse...
August 22, 2016: European Journal of Neuroscience
Ulf Simonsen, Simon Comerma-Steffensen, Karl-Erik Andersson
The currently recommended first-line treatments of erectile dysfunction, phosphodiesterase type 5 inhibitors (PDE5i), e.g. sildenafil, are efficacious in many patients with erectile dysfunction of vascular origin, but this therapy is insufficient in approximately 30-40% of men with erectile dysfunction where there is also a neuronal affection. There is a demand of novel approaches to treat the condition. We review the possibility of modulating the dopaminergic pathways to improve erectile function. Dopamine D1 (D1 , D5 )-and D2 (D2 -D4 )-like receptors in the paraventricular area, the medial preoptic area, the spinal cord, and in the erectile tissue are involved in erection, and several agonists developed for treatment of Parkinson's disease are associated with increased libido...
August 19, 2016: Basic & Clinical Pharmacology & Toxicology
Adem Can, Douglas O Frost, Roger Cachope, Joseph F Cheer, Todd D Gould
Chronic lithium treatment effectively reduces behavioral phenotypes of mania in humans and rodents. The mechanisms by which lithium exerts these actions are poorly understood. Pre-clinical and clinical evidence have implicated increased mesolimbic dopamine (DA) neurotransmission with mania. We used fast-scan cyclic voltammetry to characterize changes in extracellular DA concentrations in the nucleus accumbens (NAc) core evoked by 20 and 60 Hz electrical stimulation of the ventral tegmental area (VTA) in C57BL6/J mice treated either acutely or chronically with lithium...
August 11, 2016: Journal of Neurochemistry
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