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https://www.readbyqxmd.com/read/28531297/mechanisms-of-kappa-opioid-receptor-potentiation-of-dopamine-d2-receptor-function-in-quinpirole-induced-locomotor-sensitization-in-rats
#1
Angélica P Escobar, Marcela P González, Rodrigo C Meza, Verónica Noches, Pablo Henny, Katia Gysling, Rodrigo A España, José A Fuentealba, María E Andrés
Background: Increased locomotor activity in response to the same stimulus is an index of behavioral sensitization observed in preclinical models of drug addiction and compulsive behaviors. Repeated administration of Quinpirole (QNP), a D2/D3 dopamine agonist, induces locomotor sensitization. This effect is potentiated and accelerated by co-administration of U69593, a kappa opioid receptor agonist (KOR). The mechanism underlying KOR potentiation of QNP-induced locomotor sensitization remains to be elucidated...
May 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28531264/cariprazine-exhibits-anxiolytic-and-dopamine-d3-receptor-dependent-antidepressant-effects-in-the-chronic-stress-model
#2
Vanya Duric, Mounira Banasr, Tina Franklin, Ashley Lepack, Nika Adham, Béla Kiss, István Gyertyán, Ronald S Duman
Background: Cariprazine, a D3-preferring dopamine D2/D3 receptor partial agonist, is a new antipsychotic drug recently approved in the US for the treatment of schizophrenia and bipolar mania. We recently demonstrated that cariprazine also has significant anti-anhedonic-like effects in rats subjected to chronic stress; however, the exact mechanism of action for cariprazine's antidepressant-like properties is not known. Thus, in this study we examined whether the effects of cariprazine are mediated by dopamine D3 receptors...
May 22, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28528402/impact-of-brown-rice-specific-%C3%AE-oryzanol-on-epigenetic-modulation-of-dopamine-d2-receptors-in-brain-striatum-in-high-fat-diet-induced-obesity-in-mice
#3
Chisayo Kozuka, Tadashi Kaname, Chigusa Shimizu-Okabe, Chitoshi Takayama, Masato Tsutsui, Masayuki Matsushita, Keiko Abe, Hiroaki Masuzaki
AIMS/HYPOTHESIS: Overeating of dietary fats causes obesity in humans and rodents. Recent studies in humans and rodents have demonstrated that addiction to fats shares a common mechanism with addiction to alcohol, nicotine and narcotics in terms of a dysfunction of brain reward systems. It has been highlighted that a high-fat diet (HFD) attenuates dopamine D2 receptor (D2R) signalling in the striatum, a pivotal regulator of the brain reward system, resulting in hedonic overeating. We previously reported that the brown rice-specific bioactive constituent γ-oryzanol attenuated the preference for an HFD via hypothalamic control...
May 20, 2017: Diabetologia
https://www.readbyqxmd.com/read/28527958/treadmill-exercise-produces-neuroprotective-effects-in-a-murine-model-of-parkinson-s-disease-by-regulating-the-tlr2-myd88-nf-%C3%AE%C2%BAb-signaling-pathway
#4
Jung-Hoon Koo, Yong-Chul Jang, Dong-Ju Hwang, Hyun-Seob Um, Nam-Hee Lee, Jae-Hoon Jung, Joon-Yong Cho
Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD...
May 17, 2017: Neuroscience
https://www.readbyqxmd.com/read/28527692/regional-differences-in-dopamine-receptor-blockade-affect-timing-impulsivity-that-are-altered-by-d-amphetamine-on-differential-reinforcement-of-low-rate-responding-drl-behavior-in-rats
#5
Ruey-Kuang Cheng, Ruey-Ming Liao
The ability to control when to start an action and when to stop is crucial in human and animal behavior. A failure to suppress premature behavior or carry out an action in a timely manner is commonly seen in several neuropsychological disorders. Despite the phenomenon, the exact neural mechanisms underlying this timing impulsivity remain to be elucidated. Systemic injection of d-amphetamine (AMP) has been shown to disrupt rat's performance in the differential reinforcement of low-rate (DRL) task that requires both optimal timing and proper impulsive control as measured by peak time and non-reinforced responses, respectively...
May 17, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28527083/shared-mechanisms-of-epilepsy-migraine-and-affective-disorders
#6
Davide Zarcone, Simona Corbetta
Since the nineteenth century several clinical features have been observed in common between migraine and epilepsy (such as episodic attacks, triggering factors, presence of aura, frequent familiarity), but only in recent years researchers have really engaged in finding a common pathogenic mechanism. From studies of disease incidence, we understand how either migraine among patients with epilepsy or epilepsy among migraine patients are more frequent than in the general population. This association may result from a direct causality, by the same environmental risk factors and/or by a common genetic susceptibility...
May 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28525823/development-and-validation-of-a-reversed-phase-hplc-method-for-analysis-of-radiochemical-purity-in-123-i-ibzm
#7
Shiou-Shiow Farn, Yuen-Han Yeh, Chang-Chin Li, Ching-Shiuann Yang, Jenn-Tzong Chen, Chung-Shan Yu, Wuu-Jyh Lin
[(123)I]IBZM is used widely for in vivo imaging of D2 receptors in human brain and shows relatively fast kinetics and a greater susceptibility to synaptic dopamine release than other single-photon emission computed tomography (SPECT) radioligands. A reliable and reversed-phase HPLC method using UV/VIS and radiometric detectors has been developed for qualitative analysis of BZM and IBZM and radiochemical purity in [(123)I]IBZM preparations. The method uses gradient elution on a Zorbax XDB C-18 column with a mobile phase that consists of 10mM 3,3-dimethylglutaric acid (DMGA), pH 7...
April 15, 2017: Applied Radiation and Isotopes
https://www.readbyqxmd.com/read/28525574/a-schizophrenia-related-deletion-leads-to-kcnq2-dependent-abnormal-dopaminergic-modulation-of-prefrontal-cortical-interneuron-activity
#8
Se Joon Choi, Jun Mukai, Mirna Kvajo, Bin Xu, Anastasia Diamantopoulou, Pothitos M Pitychoutis, Bin Gou, Joseph A Gogos, Hui Zhang
Altered prefrontal cortex function is implicated in schizophrenia (SCZ) pathophysiology and could arise from imbalance between excitation and inhibition (E/I) in local circuits. It remains unclear whether and how such imbalances relate to genetic etiologies. We used a mouse model of the SCZ-predisposing 22q11.2 deletion (Df(16)A+/- mice) to evaluate how this genetic lesion affects the excitability of layer V prefrontal pyramidal neurons and its modulation by dopamine (DA). Df(16)A+/- mice have normal balance between E/I at baseline but are unable to maintain it upon dopaminergic challenge...
May 19, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28524260/presence-of-ethanol-sensitive-glycine-receptors-in-medium-spiny-neurons-in-the-mouse-nucleus-accumbens
#9
B Förstera, B Muñoz, M K Lobo, R Chandra, D M Lovinger, L G Aguayo
Alcohol abuse causes major social, economic and health-related problems worldwide. Alcohol, like other drugs of abuse, increases levels of dopamine in the nucleus accumbens, facilitating behavioural reinforcement and substance abuse. Previous studies suggested that glycine receptors (GlyRs) are involved in the regulation of accumbal dopamine levels. Here, we investigated the presence of GlyRs in accumbal dopamine receptor medium spiny neurons (MSNs) of C57BL/6J mice, analyzing mRNA expression-levels and immunoreactivity of GlyR subunits, as well as ethanol sensitivity...
May 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28523234/the-effect-of-comt-val158met-and-drd2-c957t-polymorphisms-on-executive-function-and-the-impact-of-early-life-stress
#10
Kristel Klaus, Kevin Butler, Simon J Durrant, Manir Ali, Chris F Inglehearn, Timothy L Hodgson, Humberto Gutierrez, Kyla Pennington
INTRODUCTION: Previous research has indicated that variation in genes encoding catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) may influence cognitive function and that this may confer vulnerability to the development of mental health disorders such as schizophrenia. However, increasing evidence suggests environmental factors such as early life stress may interact with genetic variants in affecting these cognitive outcomes. This study investigated the effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress in healthy adults...
May 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28522847/a-molecular-basis-for-selective-antagonist-destabilization-of-dopamine-d3-receptor-quaternary-organization
#11
Sara Marsango, Gianluigi Caltabiano, Mireia Jiménez-Rosés, Mark J Millan, John D Pediani, Richard J Ward, Graeme Milligan
The dopamine D3 receptor (D3R) is a molecular target for both first-generation and several recently-developed antipsychotic agents. Following stable expression of this mEGFP-tagged receptor, Spatial Intensity Distribution Analysis indicated that a substantial proportion of the receptor was present within dimeric/oligomeric complexes and that increased expression levels of the receptor favored a greater dimer to monomer ratio. Addition of the antipsychotics, spiperone or haloperidol, resulted in re-organization of D3R quaternary structure to promote monomerization...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28522735/d3-receptors-regulate-excitability-in-a-unique-class-of-prefrontal-pyramidal-cell
#12
Rebecca L Clarkson, Alayna T Liptak, Steven M Gee, Vikaas S Sohal, Kevin J Bender
The D3 dopamine receptor, a member of the Gi-coupled D2-family of dopamine receptors, is expressed throughout limbic circuits affected in neuropsychiatric disorders, including prefrontal cortex. These receptors are important for prefrontal executive function, as pharmacological and genetic manipulations that affect prefrontal D3 receptors alter anxiety, social interaction, and reversal learning. And yet, the mechanisms by which D3 receptors regulate prefrontal circuits, and whether D3 receptors regulate specific prefrontal subnetworks, remain unknown...
May 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28522313/neurotensin-in-the-nucleus-accumbens-reverses-dopamine-supersensitivity-evoked-by-antipsychotic-treatment
#13
Alice Servonnet, Ellie-Anna Minogianis, Claude Bouchard, Anne-Marie Bédard, Daniel Lévesque, Pierre-Paul Rompré, Anne-Noël Samaha
Long-term exposure to antipsychotics like haloperidol can increase sensitivity to dopamine agonist stimulation. This could contribute to treatment failure and increase relapse to psychosis. Chronic antipsychotic treatment elevates neurotensin levels in the nucleus accumbens (NAc), where the neuropeptide modulates dopamine function by signalling through NTS1 receptors. We hypothesized that increasing neurotensin activity in the NAc attenuates the expression of antipsychotic-induced dopamine supersensitivity, which is indicated by a potentiated psychomotor response to amphetamine...
May 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28521704/dopamine-d2-receptors-dimers-how-can-we-pharmacologically-target-them
#14
Marco Carlia, Shivakumar Kolachalam, Stefano Aringhieri, Mario Rossib, Luca Giovannini, Roberto Maggio, Marco Scarselli
Dopamine D2 and D3 receptors are important pharmacological targets in Schizophrenia and Parkinson's disease. Intriguingly, many studies have shown that they form homo- and heterodimers, and they can be targeted in specific tissues with new drugs. In this direction, many efforts have been made to develop new molecules that are able to interact with these receptor dimeric complexes. Among various strategies for targeting dopamine receptors dimers, two distinct classes of compounds, such as bivalent and bitopic ligands, have gained particular attention and their use in pharmacology looks promising...
May 18, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28521372/synthesis-and-characterization-of-new-azecine-derivatives-as-potential-neuroleptics
#15
Stephanie Zergiebel, Christian Fleck, Hans-Dieter Arndt, Christoph Enzensperger, Andreas Seeling
Dibenzo- and benzindolo-azecines represent a class of potential neuroleptics. To characterize the effectiveness at the dopamine and 5-HT2A-receptor representative structures were synthesized and tested by radio ligand binding studies, in vivo and in vitro studies.Neuroleptic potency and the risk of side effects of the prodrug 7-methyl-5,6,7,8,9,14-hexahydrodibenzo[d,g]azecin-3-yl isobutyrate, an ester derivative of the most promising azecine 7-methyl-5,6,7,8,9,14-hexahydrodibenzo[d,g]azecin-3-ol (LE404), was tested in vivo concerning conditioned avoidance response inhibition, locomotor activity and triggering of catalepsy vs...
May 18, 2017: Drug Research
https://www.readbyqxmd.com/read/28520722/altered-detrusor-contractility-in-mptp-treated-common-marmosets-with-bladder-hyperreflexia
#16
Sara Pritchard, Michael J Jackson, Atsuko Hikima, Lisa Lione, Christopher D Benham, K Ray Chaudhuri, Sarah Rose, Peter Jenner, Mahmoud M Iravani
Bladder hyperreflexia is a common non-motor feature of Parkinson's disease. We now report on the contractility of the isolated primate detrusor strips devoid of nerve input and show that following MPTP, the amplitude and frequency of spontaneous contraction was increased. These responses were unaffected by dopamine D1 and D2 receptor agonists A77636 and ropinirole respectively. Contractions by exogenous carbachol, histamine or ATP were similar and no differences in the magnitude of noradrenaline-induced relaxation were seen in detrusor strip obtained from normal and MPTP-treated common marmosets (Callithrix jacchus)...
2017: PloS One
https://www.readbyqxmd.com/read/28516479/g%C3%AE-s-signalling-of-the-cb1-receptor-and-the-influence-of-receptor-number
#17
David B Finlay, Erin E Cawston, Natasha L Grimsey, Morag R Hunter, Anisha Korde, V Kiran Vemuri, Alexandros Makriyannis, Michelle Glass
BACKGROUND AND PURPOSE: CB1 cannabinoid receptor signalling is canonically mediated through inhibitory Gαi proteins, but signalling through other G proteins occurs under some circumstances; Gαs being the most characterised secondary pathway. Determinants of this signalling switch identified to date include Gαi blockade, CB1 /D2 dopamine receptor co-stimulation, CB1 agonist class, and cell background. The aim of this study was to examine the effects of receptor number and ligand dependence on CB1 signalling...
May 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28516430/ramelteon-improves-post-traumatic-stress-disorder-like-behaviors-exhibited-by-fatty-acid-binding-protein-3-null-mice
#18
Yasushi Yabuki, Ibuki Takahata, Kazuya Matsuo, Yuji Owada, Kohji Fukunaga
We previously reported that fatty acid-binding protein 3 (FABP3) knockout (Fabp3 (-/-)) mice exhibit abnormal dopamine-related behaviors such as enhanced dopamine D2 receptor antagonist-induced catalepsy behaviors. Here, we report that Fabp3 null mice exhibit cognitive deficits, hyperlocomotion and impaired fear extinction, and thus show post-traumatic stress disorder (PTSD)-like behaviors. Notably, chronic administration of ramelteon (1.0 mg/kg, p.o.), a melatonin receptor agonist, improved all PTSD-like behaviors tested in Fabp3 (-/-) mice...
May 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28515684/selegiline-ameliorates-depression-like-behavior-in-mice-lacking-the-cd157-bst1-gene-a-risk-factor-for-parkinson-s-disease
#19
Satoka Kasai, Toru Yoshihara, Olga Lopatina, Katsuhiko Ishihara, Haruhiro Higashida
Parkinson's disease (PD), a neurodegenerative disorder, is accompanied by various non-motor symptoms including depression and anxiety, which may precede the onset of motor symptoms. Selegiline is an irreversible monoamine oxidase-B (MAO-B) inhibitor, and is widely used in the treatment of PD and major depression. However, there are few reports about the effects of selegiline on non-motor symptoms in PD. The aim of this study was to explore the antidepressant and anxiolytic effects of selegiline, using CD157/BST1 knockout (CD157 KO) mouse, a PD-related genetic model displaying depression and anxiety, compared with other antiparkinsonian drugs and an antidepressant, and was to investigate the effects of selegiline on biochemical parameters in emotion-related brain regions...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28515088/loss-of-nherf-1-expression-prevents-dopamine-mediated-na-k-atpase-regulation-in-renal-proximal-tubule-cells-from-rat-models-of-hypertension-aged-f344-and-shrs
#20
Michelle T Barati, Corey J Ketchem, Michael L Merchant, Walter B Kusiak, Pedro A Jose, Edward J Weinman, Amanda J LeBlanc, Eleanor D Lederer, Syed J Khundmiri
Dopamine decreases Na-K ATPase (NKA) activity by PKC-dependent phosphorylation and endocytosis of the NKA alpha1. Dopamine-mediated regulation of NKA is impaired in aging and some forms of hypertension. Using opossum (OK) proximal tubule cells (PTCs), we demonstrated that sodium-hydrogen exchanger regulatory factor-1 (NHERF-1) associates with NKA alpha1 and dopamine-1 receptor (D1R). This association is required for the dopamine-mediated regulation of NKA. In OK cells dopamine decreases NHERF-1 association with NKA alpha1 but increases its association with D1R...
May 17, 2017: American Journal of Physiology. Cell Physiology
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