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EJN Table of Content

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  • Issue Cover

    1. Issue Cover (January 2017) (page i)

      Version of Record online: 2 JAN 2017 | DOI: 10.1111/ejn.13433

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      Cover image by Harald Sitte and Matthäus Willeit


    1. Introduction to the Special Issue on dopamine celebrating the 90th birthday of Oleh Hornykiewicz (page 1)

      Harald Sitte and Matthäus Willeit

      Version of Record online: 2 JAN 2017 | DOI: 10.1111/ejn.13502


    1. The dopamine D3 receptor, a quarter century later (pages 2–19)

      Pierre Sokoloff and Bernard Le Foll

      Version of Record online: 3 OCT 2016 | DOI: 10.1111/ejn.13390

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      This review updates the existing knowledge suggesting a role in schizophrenia and drug addiction for the D3 receptor, which is expressed in brain regions controlling reward, emotions and motivation and modulates glutamatergic pathways from the prefrontal cortex to subcortical areas. The clinical potency of selective D3 compounds still await confirmation and their development will benefit from initial assessment of target engagement through the use of PET.

    2. Membrane transporters as mediators of synaptic dopamine dynamics: implications for disease (pages 20–33)

      Kelly M. Lohr, Shababa T. Masoud, Ali Salahpour and Gary W. Miller

      Version of Record online: 2 SEP 2016 | DOI: 10.1111/ejn.13357

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      This review describes the importance of the dopamine transporter (DAT) and the vesicular monoamine transporter 2 (VMAT2) on dopamine compartmentalization and neuronal health (A–C). While theoretical, this schematic highlights emerging evidence from mouse models of varying transporter levels. We predict that the continuum of transporter function in these animal models will allow for new discoveries concerning endogenous dopamine handling, pharmacological manipulation of the transporters, and dopamine‐dependent behaviors (D).

    3. Decision‐making in chronic ecstasy users: a systematic review (pages 34–44)

      Felix Betzler, Leonard Viohl and Nina Romanczuk‐Seiferth

      Version of Record online: 15 DEC 2016 | DOI: 10.1111/ejn.13480

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      MDMA—a popular club drug better known as ecstasy and controversially discussed as a potential therapeutic agent. Therapeutic use, however, requires a thorough knowledge of its influence on decision‐making: impulsivity as well as tendencies toward risky decision‐making among long‐term MDMA users can be found, although polydrug users show similar behavior. Thus, in this review article, current state of knowledge on decision‐making in chronic ecstasy users and possible implications are discussed.

    4. Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence (pages 45–57)

      Ulrich Sauerzopf, Roberto Sacco, Gaia Novarino, Marco Niello, Ana Weidenauer, Nicole Praschak‐Rieder, Harald Sitte and Matthäus Willeit

      Version of Record online: 19 OCT 2016 | DOI: 10.1111/ejn.13418

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      We have reviewed 19 publications on reprogrammed cells derived from patients with schizophrenia and five publications on cells derived from patients with bipolar disorder. This review summarizes findings suggesting alterations in synaptic transmission, neuro‐development and energy metabolism observed in induced pluripotent stem cells, neuronal progenitor cells and induced neuron‐like cells.

    5. Brain dopamine neurone ‘damage’: methamphetamine users vs. Parkinson's disease – a critical assessment of the evidence (pages 58–66)

      Stephen J. Kish, Isabelle Boileau, Russell C. Callaghan and Junchao Tong

      Version of Record online: 5 SEP 2016 | DOI: 10.1111/ejn.13363

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      Striatal dopamine (DA) marker changes in Parkinson's disease (PD) vs. methamphetamine (MA) users. In autopsied brain of persons with PD, striatal levels of all DA markers (DA and metabolites DOPAC, HVA and 3‐MT, synthesizing enzymes TH and AADC, and transporters VMAT2 and DAT) are low, whereas in MA users, only two markers (DA and DAT) are below normal. This suggests that any loss of brain dopamine neurones in at least a subgroup of recreational MA users, if at all present, might not be substantial.

    6. Pathological gambling in Parkinson's disease: what are the risk factors and what is the role of impulsivity? (pages 67–72)

      Petra Heiden, Andreas Heinz and Nina Romanczuk‐Seiferth

      Version of Record online: 1 OCT 2016 | DOI: 10.1111/ejn.13396

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      The incidence of pathological gambling in Parkinson's patients is significantly greater than in the general population. This review summarizes evidence in this field of research attempting to reveal the relationship between Parkinson therapy and pathological gambling, discusses the reasons why some patients react on them differently than others, what the relevant risk factors are and considers how impulsivity may contribute to the development of gambling symptoms.

    7. l‐DOPA‐induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role? (pages 73–91)

      Anna R. Carta, Giovanna Mulas, Mariza Bortolanza, Terence Duarte, Elisabetta Pillai, Gilberto Fisone, Rita Raisman Vozari and Elaine Del‐Bel

      Version of Record online: 9 DEC 2016 | DOI: 10.1111/ejn.13482

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      l‐DOPA‐induced dyskinesia (LID) is associated with striatal inflammatory responses, with chronically activated microglia and astrocytes, and overproduction of cytokines and NO. LID is modulated by agents increasing or decreasing neuroinflammation. Microglia and astrocytes‐released cytokines modulate synaptic function. Excessive release of inflammatory cytokines in the striatum may lead to an aberrant neuron‐glia cross‐talk by affecting synaptic activity, thereby contributing to LID development.


    1. On the properties of identified dopaminergic neurons in the mouse substantia nigra and ventral tegmental area (pages 92–105)

      Paraskevi Krashia, Alessandro Martini, Annalisa Nobili, Daniela Aversa, Marcello D'Amelio, Nicola Berretta, Ezia Guatteo and Nicola Biagio Mercuri

      Version of Record online: 11 SEP 2016 | DOI: 10.1111/ejn.13364

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      We studied the properties of identified DAergic neurons in midbrain slices from TH‐GFP mice. We saw that the firing rate, membrane properties, cell size and Ih magnitude of TH‐GFP+ cells varied with a mediolateral gradient across distinct SNpc and VTA subregions. TH‐GFP+ cells were inhibited by DA and excited by Met‐Enk, whereas Zd7288 inhibited firing only in the most lateral regions. Our work provides new insights into the variability in midbrain DAergic neurons along the mediolateral axis.

    2. Gonadectomy but not biological sex affects burst‐firing in dopamine neurons of the ventral tegmental area and in prefrontal cortical neurons projecting to the ventral tegmentum in adult rats (pages 106–120)

      Mallory N. Locklear, Michalis Michealos, William F. Collins and Mary F. Kritzer

      Version of Record online: 19 SEP 2016 | DOI: 10.1111/ejn.13380

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      Single unit recordings made in ventral tegmental area dopamine neurons and in ventral tegmentally projecting prefrontal cortex cells were compared among urethane‐anaesthetized male, female and gonadectomized male rats. A survey of firing properties showed that gonadectomy selectively increased burst firing in both areas in a testosterone‐sensitive, estradiol‐insensitive manner. A working model is proposed for androgen impact originating in cortex and feeding forward to the ventral midbrain.

    3. Preserved dopaminergic homeostasis and dopamine‐related behaviour in hemizygous TH‐Cre mice (pages 121–128)

      Annika H. Runegaard, Kathrine L. Jensen, Ciarán M. Fitzpatrick, Ditte Dencker, Pia Weikop, Ulrik Gether and Mattias Rickhag

      Version of Record online: 22 AUG 2016 | DOI: 10.1111/ejn.13347

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      Phenotypic characterization of the TH‐Cre mouse strain validates its use to target and study the dopamine system. Hemizygous TH‐Cre mice display preserved dopaminergic homeostasis with unaltered levels of TH and dopamine as well as unaffected dopamine turnover in striatum. TH‐Cre mice demonstrate normal responses in basic behavioural paradigms related to dopaminergic signalling (Sagittal and coronal brain sections in illustration were modified from Paxinos and Franklin, 2001).

    4. Reversal learning strategy in adolescence is associated with prefrontal cortex activation (pages 129–137)

      Rebecca Boehme, Robert C. Lorenz, Tobias Gleich, Lydia Romund, Patricia Pelz, Sabrina Golde, Eva Flemming, Andrew Wold, Lorenz Deserno, Joachim Behr, Diana Raufelder, Andreas Heinz and Anne Beck

      Version of Record online: 5 OCT 2016 | DOI: 10.1111/ejn.13401

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      Adolescents who use task structure when solving a reversal learning task show higher prefrontal activation related to prediction errors compared to those who rely less on task structure. PE‐related activity is associated with pubertal development in prefrontal areas, insula and anterior cingulate.

    5. Dopamine receptor activity participates in hippocampal synaptic plasticity associated with novel object recognition (pages 138–146)

      Kechun Yang, John I. Broussard, Amber T. Levine, Daniel Jenson, Benjamin R. Arenkiel and John A. Dani

      Version of Record online: 1 OCT 2016 | DOI: 10.1111/ejn.13406

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      Novel object recognition (NOR) engages the hippocampus as mice remember previously presented objects as an indication of learning. In this study, Yang et al. measured the ratio of AMPA to NMDA currents. When mice were exposed to novel objects (right), the AMPA/NMDA ratio increased in dentate granule neurons. Accurately performing the task and the associated increase in the AMPA/NMDA ratio were dependent upon D1‐like receptor activity.

    6. Dopaminergic neurotransmission in ventral and dorsal striatum differentially modulates alcohol reinforcement (pages 147–158)

      Marcia Spoelder, Peter Hesseling, Matthew Styles, Annemarie M. Baars, José G. Lozeman‐van ‘t Klooster, Heidi M. B. Lesscher and Louk J. M. J. Vanderschuren

      Version of Record online: 7 SEP 2016 | DOI: 10.1111/ejn.13358

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      We assessed how dopamine within striatal sub‐regions modulates alcohol reinforcement, using bilateral infusions of the dopamine receptor antagonist alpha‐flupenthixol. Our results suggest that dopaminergic neurotransmission in the nucleus accumbens (NAcc) shell is involved in the incentive motivation for alcohol, while NAcc core dopamine plays a more general role in alcohol reinforcement. Dorsolateral striatal dopamine comes into play when obtaining alcohol requires high levels of effort.

    7. Chronic D2/3 agonist ropinirole treatment increases preference for uncertainty in rats regardless of baseline choice patterns (pages 159–166)

      Melanie Tremblay, Mason M. Silveira, Sukhbir Kaur, Jay G. Hosking, Wendy K. Adams, Christelle Baunez and Catharine A. Winstanley

      Version of Record online: 11 AUG 2016 | DOI: 10.1111/ejn.13332

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      Here, we report that chronic administration of the D2/3 receptor agonist ropinirole increased preference for uncertainty on a rat model of gambling‐like behaviour, the rodent betting task (rBT), in both healthy rats and in a 6‐OHDA lesion model of early‐stage Parkinson's disease (PD). This suggests that D2/3 agonist‐induced impulse control disorders (ICDs) are caused by drug treatment independent from pre‐morbid behaviours or PD itself.

    8. The unique psychostimulant profile of (±)‐modafinil: investigation of behavioral and neurochemical effects in mice (pages 167–174)

      Maddalena Mereu, Lauren E. Chun, Thomas E. Prisinzano, Amy H. Newman, Jonathan L. Katz and Gianluigi Tanda

      Version of Record online: 11 SEP 2016 | DOI: 10.1111/ejn.13376

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      Modafinil, like cocaine, increased nucleus accumbens dopamine (DA) levels, produced cocaine‐like discriminative‐stimulus (subjective) effects and enhanced those effects when administered with cocaine. Nonetheless, modafinil is unique. Its lower dopaminergic potency and efficacy than cocaine, with subjective effects obtained at lower doses and earlier onset times than expected from effects on DA, suggest that non‐dopaminergic effects may be critical in modafinil's unique pharmacologic profile.

    9. Modelling idiopathic Parkinson disease as a complex illness can inform incidence rate in healthy adults: the PREDIGT score (pages 175–191)

      Michael G. Schlossmacher, Julianna J. Tomlinson, Goncalo Santos, Bojan Shutinoski, Earl G. Brown, Douglas Manuel and Tiago Mestre

      Version of Record online: 27 DEC 2016 | DOI: 10.1111/ejn.13476

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      The PREDIGT score quantifies the probability for the risk (PR) of Parkinson disease (PD) as a function of five factors: E (Exposome); D (Genetics); I (Initiation); G (Sex/Gender); and T (Time). The disease projection curve for a case of idiopathic PD is shown (solid line), where a PR of 100% is reached at 66 years of age. The curve shifts based on values for the five factors, thus changing the incidence risk at a given age, for example, to a PR = 80% at 52 years, 70% at 72 years and 60% at 88 years.

    10. Dopamine and noradrenaline, but not serotonin, in the human claustrum are greatly reduced in patients with Parkinson's disease: possible functional implications (pages 192–197)

      Harald H. Sitte, Christian Pifl, Ali H. Rajput, Heide Hörtnagl, Junchao Tong, George K. Lloyd, Stephen J. Kish and Oleh Hornykiewicz

      Version of Record online: 11 NOV 2016 | DOI: 10.1111/ejn.13435

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      In the human brain, the claustrum is a small subcortical telencephalic nucleus, situated between the insular cortex and the putamen. We examined the behaviour of the classical monoamine neurotransmitters in the claustrum of the normal autopsied human brain and of patients who died with idiopathic Parkinson's disease (PD). In patients, we found the levels of dopamine and noradrenaline to be greatly reduced in comparison to control. We propose that loss of dopamine and noradrenaline in the PD claustrum is critical in the aetiology of both the motor and the non‐motor symptoms of PD.

    11. Coupling of D2R Short but not D2R Long receptor isoform to the Rho/ROCK signaling pathway renders striatal neurons vulnerable to mutant huntingtin (pages 198–206)

      Beatriz Galan‐Rodriguez, Elodie Martin, Emmanuel Brouillet, Nicole Déglon, Sandrine Betuing and Jocelyne Caboche

      Version of Record online: 24 OCT 2016 | DOI: 10.1111/ejn.13415

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      Specific coupling of D2R Short to Rho/Rock signaling and striatal vulnerability in Huntington's Disease.

    12. A Caenorhabditis elegans model to study dopamine transporter deficiency syndrome (pages 207–214)

      Placido Illiano, Ambra Lanzo, Damiana Leo, Maria Paglione, Giuseppina Zampi, Raul R. Gainetdinov and Elia Di Schiavi

      Version of Record online: 2 SEP 2016 | DOI: 10.1111/ejn.13366

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      Caenorhabditis elegans dopamine transporter (DAT) orthologue, cedat‐1, maintains homeostasis in dopamine (DA) signalling. cedat‐1 knockout (KO) causes accumulation of extracellular DA‐inducing swimming‐induced paralysis (SWIP). Expression of human DAT (hDATwt) in cedat‐1 KO rescues SWIP defects, whereas dopamine transporter deficiency syndrome‐related mutations in hDAT (hDATmut) do not, or only partially, rescue the SWIP defects. We provide a new in vivo tool for investigating mutations in hDAT gene found in DTDS patients.

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