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Dopamine and effort

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https://www.readbyqxmd.com/read/27926449/the-role-of-dopamine-in-the-pathophysiology-and-treatment-of-apathy
#1
T T-J Chong, M Husain
Disorders of diminished motivation, such as apathy, are common and prevalent across a wide range of medical conditions, including Parkinson's disease, Alzheimer's dementia, stroke, depression, and schizophrenia. Such disorders have a significant impact on morbidity and quality of life, yet their management lacks consensus and remains unsatisfactory. Here, we review laboratory and clinical evidence for the use of dopaminergic therapies in the treatment of apathy. Dopamine is a key neurotransmitter that regulates motivated decision making in humans and other species...
2016: Progress in Brain Research
https://www.readbyqxmd.com/read/27910188/comparing-rewarding-and-reinforcing-properties-between-bath-salt-3-4-methylenedioxypyrovalerone-mdpv-and-cocaine-using-ultrasonic-vocalizations-in-rats
#2
Steven J Simmons, Ryan A Gregg, Fionya H Tran, Lili Mo, Eva von Weltin, David J Barker, Taylor A Gentile, Lucas R Watterson, Scott M Rawls, John W Muschamp
Abuse of synthetic psychostimulants like synthetic cathinones has risen in recent years. 3,4-Methylenedioxypyrovalerone (MDPV) is one such synthetic cathinone that demonstrates a mechanism of action similar to cocaine. Compared to cocaine, MDPV is more potent at blocking dopamine and norepinephrine reuptake and is readily self-administered by rodents. The present study compared the rewarding and reinforcing properties of MDPV and cocaine using systemic injection dose-response and self-administration models...
December 1, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27908561/beyond-eye-gaze-what-else-can-eyetracking-reveal-about-cognition-and-cognitive-development
#3
REVIEW
Maria K Eckstein, Belén Guerra-Carrillo, Alison T Miller Singley, Silvia A Bunge
This review provides an introduction to two eyetracking measures that can be used to study cognitive development and plasticity: pupil dilation and spontaneous blink rate. We begin by outlining the rich history of gaze analysis, which can reveal the current focus of attention as well as cognitive strategies. We then turn to the two lesser-utilized ocular measures. Pupil dilation is modulated by the brain's locus coeruleus-norepinephrine system, which controls physiological arousal and attention, and has been used as a measure of subjective task difficulty, mental effort, and neural gain...
November 11, 2016: Developmental Cognitive Neuroscience
https://www.readbyqxmd.com/read/27882999/activation-of-ventral-tegmental-area-5-ht2c-receptors-reduces-incentive-motivation
#4
Lourdes Valencia-Torres, Cristian M Olarte-Sánchez, David J Lyons, Teodora Georgescu, Megan Greenwald-Yarnell, Martin G Myers, Christopher M Bradshaw, Lora K Heisler
Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT2CR) is a target for the treatment of human obesity. Mechanistically, 5-HT2CRs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HT2CRs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice...
November 24, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27860462/improved-anticancer-photothermal-therapy-using-the-bystander-effect-enhanced-by-antiarrhythmic-peptide-conjugated-dopamine-modified-reduced-graphene-oxide-nanocomposite
#5
Jiantao Yu, Yu-Hsin Lin, Lingyan Yang, Chih-Ching Huang, Liliang Chen, Wen-Cheng Wang, Guan-Wen Chen, Junyan Yan, Saranta Sawettanun, Chia-Hua Lin
Despite tremendous efforts toward developing novel near-infrared (NIR)-absorbing nanomaterials, improvement in therapeutic efficiency remains a formidable challenge in photothermal cancer therapy. This study aims to synthesize a specific peptide conjugated polydopamine-modified reduced graphene oxide (pDA/rGO) nanocomposite that promotes the bystander effect to facilitate cancer treatment using NIR-activated photothermal therapy. To prepare a nanoplatform capable of promoting the bystander effect in cancer cells, we immobilized antiarrhythmic peptide 10 (AAP10) on the surface of dopamine-modified rGO (AAP10-pDA/rGO)...
November 8, 2016: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/27859866/modeling-idiopathic-parkinson-disease-as-a-complex-illness-can-inform-incidence-risk-in-healthy-adults-the-pr-edigt-score
#6
Michael G Schlossmacher, Julianna J Tomlinson, Goncalo Santos, Bojan Shutinoski, Earl G Brown, Douglas Manuel, Tiago Mestre
Fifty-five years after the concept of dopamine replacement therapy was introduced, Parkinson disease (PD) remains an incurable neurological disorder. To date, no disease-modifying therapeutic has been approved. The inability to predict PD incidence risk in healthy adults is seen as one limitation in drug development, because by the time of clinical diagnosis >60% of dopamine neurons have been lost. We have designed an incidence prediction model founded on the concept that the pathogenesis of PD is similar to that of many disorders observed in ageing humans, i...
November 12, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27853270/loss-of-nmda-receptors-in-dopamine-neurons-leads-to-the-development-of-affective-disorder-like-symptoms-in-mice
#7
Kamila Jastrzębska, Magdalena Walczak, Przemysław Eligiusz Cieślak, Łukasz Szumiec, Mateusz Turbasa, David Engblom, Tomasz Błasiak, Jan Rodriguez Parkitna
The role of changes in dopamine neuronal activity during the development of symptoms in affective disorders remains controversial. Here, we show that inactivation of NMDA receptors on dopaminergic neurons in adult mice led to the development of affective disorder-like symptoms. The loss of NMDA receptors altered activity and caused complete NMDA-insensitivity in dopamine-like neurons. Mutant mice exhibited increased immobility in the forced swim test and a decrease in social interactions. Mutation also led to reduced saccharin intake, however the preference of sweet taste was not significantly decreased...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27807030/aging-affects-dopaminergic-neural-mechanisms-of-cognitive-flexibility
#8
Anne S Berry, Vyoma D Shah, Suzanne L Baker, Jacob W Vogel, James P O'Neil, Mustafa Janabi, Henry D Schwimmer, Shawn M Marks, William J Jagust
: Aging is accompanied by profound changes in the brain's dopamine system that affect cognitive function. Evidence of powerful individual differences in cognitive aging has sharpened focus on identifying biological factors underlying relative preservation versus vulnerability to decline. Dopamine represents a key target in these efforts. Alterations of dopamine receptors and dopamine synthesis are seen in aging, with receptors generally showing reduction and synthesis demonstrating increases...
November 2, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27805392/discovery-of-g-protein-biased-d2-dopamine-receptor-partial-agonists
#9
Xin Chen, John D McCorvy, Matthew G Fischer, Kyle V Butler, Yudao Shen, Bryan L Roth, Jian Jin
Biased ligands (also known as functionally selective ligands) of G protein-coupled receptors are valuable tools for dissecting the roles of G protein-dependent and independent signaling pathways in health and disease. Biased ligands have also been increasingly pursued by the biomedical community as promising therapeutics with improved efficacy and reduced side effects compared with unbiased ligands. We previously discovered first-in-class β-arrestin-biased agonists of dopamine D2 receptor (D2R) by extensively exploring multiple regions of aripiprazole, a balanced D2R agonist...
November 2, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27798138/a-gabaergic-projection-from-the-centromedial-nuclei-of-the-amygdala-to-ventromedial-prefrontal-cortex-modulates-reward-behavior
#10
Dong-Oh Seo, Samuel C Funderburk, Dionnet L Bhatti, Laura E Motard, Dillan Newbold, Kasey S Girven, Jordan G McCall, Michael Krashes, Dennis R Sparta, Michael R Bruchas
: The neural circuitry underlying mammalian reward behaviors involves several distinct nuclei throughout the brain. It is widely accepted that the midbrain dopamine (DA) neurons are critical for the reward-related behaviors. Recent studies have shown that the centromedial nucleus of the amygdala (CeMA) has a distinct role in regulating reward-related behaviors. However, the CeMA and ventromedial PFC (vmPFC) interaction in reward regulation remains poorly understood. Here, we identify and dissect a GABAergic projection that originates in the CeMA and terminates in the vmPFC (VGat-Cre(CeMA-vmPFC)) using viral-vector-mediated, cell-type-specific optogenetic techniques in mice...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27779245/association-between-drd2-and-drd3-gene-polymorphisms-and-gastrointestinal-symptoms-induced-by-levodopa-therapy-in-parkinson-s-disease
#11
M Rieck, A F Schumacher-Schuh, V Altmann, S M Callegari-Jacques, C R M Rieder, M H Hutz
Levodopa is the most used drug to treat motor symptoms in Parkinson's disease (PD). However, dopaminergic side effects such as nausea and vomiting may occur. Several evidences indicate a major role for dopamine receptors D2 (DRD2) and D3 (DRD3) in emetic activity. The aim of this study was to investigate the relationship of DRD2 rs1799732 and DRD3 rs6280 gene polymorphisms with gastrointestinal (GI) symptoms induced by levodopa in PD patients. Two hundred and seventeen PD patients on levodopa therapy were investigated...
October 25, 2016: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/27761108/dopamine-d3-receptor-antagonists-as-potential-therapeutics-for-the-treatment-of-neurological-diseases
#12
Samuele Maramai, Sandra Gemma, Simone Brogi, Giuseppe Campiani, Stefania Butini, Holger Stark, Margherita Brindisi
D3 receptors represent a major focus of current drug design and development of therapeutics for dopamine-related pathological states. Their close homology with the D2 receptor subtype makes the development of D3 selective antagonists a challenging task. In this review, we explore the relevance and therapeutic utility of D3 antagonists or partial agonists endowed with multireceptor affinity profile in the field of central nervous system disorders such as schizophrenia and drug abuse. In fact, the peculiar distribution and low brain abundance of D3 receptors make them a valuable target for the development of drugs devoid of motor side effects classically elicited by D2 antagonists...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27736881/forgetting-in-reinforcement-learning-links-sustained-dopamine-signals-to-motivation
#13
Ayaka Kato, Kenji Morita
It has been suggested that dopamine (DA) represents reward-prediction-error (RPE) defined in reinforcement learning and therefore DA responds to unpredicted but not predicted reward. However, recent studies have found DA response sustained towards predictable reward in tasks involving self-paced behavior, and suggested that this response represents a motivational signal. We have previously shown that RPE can sustain if there is decay/forgetting of learned-values, which can be implemented as decay of synaptic strengths storing learned-values...
October 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27732870/the-effects-of-reduced-dopamine-transporter-function-and-chronic-lithium-on-motivation-probabilistic-learning-and-neurochemistry-in-mice-modeling-bipolar-mania
#14
Morgane Milienne-Petiot, James P Kesby, Mary Graves, Jordy van Enkhuizen, Svetlana Semenova, Arpi Minassian, Athina Markou, Mark A Geyer, Jared W Young
BACKGROUND: Bipolar disorder (BD) mania patients exhibit poor cognition and reward-seeking/hypermotivation, negatively impacting a patient's quality of life. Current treatments (e.g., lithium), do not treat such deficits. Treatment development has been limited due to a poor understanding of the neural mechanisms underlying these behaviors. Here, we investigated putative mechanisms underlying cognition and reward-seeking/motivational changes relevant to BD mania patients using two validated mouse models and neurochemical analyses...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27633376/improving-current-treatments-for-schizophrenia
#15
Nadja P Maric, Milica J Jovicic, Marina Mihaljevic, Cedo Miljevic
Preclinical Research After the identification of the schizophrenia as an illness over a century ago, treatment of affected individuals included unspecific, mostly very robust methods including deep insulin coma and lobectomy/leucotomy. The first relatively specific treatment of schizophrenia started about 60 years ago with the antipsychotic chlorpromazine. All currently approved antipsychotic drugs block dopamine receptors, indicating that manipulation of dopaminergic function is fundamental to a therapeutic response in psychosis...
November 2016: Drug Development Research
https://www.readbyqxmd.com/read/27629704/dopamine-manipulation-affects-response-vigor-independently-of-opportunity-cost
#16
Alexandre Zénon, Sophie Devesse, Etienne Olivier
UNLABELLED: Dopamine is known to be involved in regulating effort investment in relation to reward, and the disruption of this mechanism is thought to be central in some pathological situations such as Parkinson's disease, addiction, and depression. According to an influential model, dopamine plays this role by encoding the opportunity cost, i.e., the average value of forfeited actions, which is an important parameter to take into account when making decisions about which action to undertake and how fast to execute it...
September 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27608362/progesterone-the-neglected-hormone-in-schizophrenia-a-focus-on-progesterone-dopamine-interactions
#17
Jeehae Sun, Adam J Walker, Brian Dean, Maarten van den Buuse, Andrea Gogos
Sex differences appear to be an important factor in schizophrenia. Women with schizophrenia tend to exhibit less disease impairment than men, typically presenting with a later age-at-onset, lower overall incidence and less severe symptoms. These observations underpin the estrogen hypothesis of schizophrenia, which postulates a protective role of estrogen against the development and severity of the disorder. While there has been significant attention placed on the impact of estrogens in schizophrenia, less consideration has been afforded to the role of progesterone, the other main female gonadal hormone...
August 24, 2016: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/27604387/the-roles-of-the-anterior-cingulate-cortex-and-its-dopamine-receptors-in-self-paced-cost-benefit-decision-making-in-rats
#18
Shuai Wang, Shan-Hu Hu, Yi Shi, Bao-Ming Li
It has been shown that the anterior cingulate cortex (ACC) and its dopamine system are crucial for decision making that requires physical/emotional effort, but not for all forms of cost-benefit decision making. Previous studies had mostly employed behavioral tasks with two competing cost-reward options that were preset by the experimenters. However, few studies have been conducted using scenarios in which the subjects have full control over the energy/time expenditure required to obtain a proportional reward...
September 7, 2016: Learning & Behavior
https://www.readbyqxmd.com/read/27521051/dopaminergic-neurotransmission-in-ventral-and-dorsal-striatum-differentially-modulates-alcohol-reinforcement
#19
Marcia Spoelder, Peter Hesseling, Matthew Styles, Annemarie M Baars, José G Lozeman-van 't Klooster, Heidi M B Lesscher, Louk J M J Vanderschuren
Dopaminergic neurotransmission in the striatum has been widely implicated in the reinforcing properties of substances of abuse. However, the striatum is functionally heterogeneous, and previous work has mostly focused on psychostimulant drugs. Therefore, we investigated how dopamine within striatal sub-regions modulates alcohol-directed behaviour in rats. We assessed the effects of infusion of the dopamine receptor antagonist alpha-flupenthixol into the shell and core of the nucleus accumbens (NAcc) and the dorsolateral striatum (DLS) on responding for alcohol under fixed ratio 1 (FR1) and progressive ratio (PR) schedules of reinforcement...
August 13, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27502054/pilot-clinical-observations-between-food-and-drug-seeking-derived-from-fifty-cases-attending-an-eating-disorder-clinic
#20
Harriet Beitscher-Campbell, Kenneth Blum, Marcelo Febo, Margaret A Madigan, John Giordano, Rajendra D Badgaiyan, Eric R Braverman, Kristina Dushaj, Mona Li, Mark S Gold
Background The reward deficiency syndrome hypothesis posits that genes are responsible for reward dependence and related behaviors. There is evidence that both bulimia and anorexia nervosa, especially in women, have been linked to a lifetime history of substance use disorder (SUD). There are difficulties in accepting food as an addiction similar to drugs; however, increasingly neuroimaging studies favor such an assertion. Case presentations We are reporting the evidence of comorbidity of eating disorders with SUD found within these case presentations...
September 2016: Journal of Behavioral Addictions
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