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https://www.readbyqxmd.com/read/29116599/the-class-a-gpcr-dopamine-d2-receptor-forms-transient-dimers-stabilized-by-agonists-detection-by-single-molecule-tracking
#1
Rinshi S Kasai, Shuichi V Ito, Ryo M Awane, Takahiro K Fujiwara, Akihiro Kusumi
Whether class-A G-protein coupled receptors (GPCRs) exist and work as monomers or dimers has drawn extensive attention. A class-A GPCR dopamine D2 receptor (D2R) is involved in many physiological and pathological processes and diseases, indicating its critical role in proper functioning of neuronal circuits. In particular, D2R homodimers might play key roles in schizophrenia development and amphetamine-induced psychosis. Here, using single-molecule imaging, we directly tracked single D2R molecules in the plasma membrane at a physiological temperature of 37 °C, and unequivocally determined that D2R forms transient dimers with a lifetime of 68 ms in its resting state...
November 7, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29065847/long-term-administration-of-antipsychotic-drugs-in-schizophrenia-and-influence-of-substance-and-drug-abuse-on-the-disease-outcome
#2
F-M Werner, Rafael Coveñas
BACKGROUND: Many schizophrenic patients with a long-term administration of antipsychotic drugs do not regularly adhere to the prescribed pharmacotherapy. Antipsychotic drugs constitute a palliative, but not a curative treatment, and the long-term effect of these drugs is not secure. Patients tend to consume nicotine and alcohol, as well as some patients consume drugs such as cannabis and amphetamines. OBJECTIVE: The objective of this mini-review is to examine the reasons for the high tendency of schizophrenic patients to consume alcohol, nicotine and drugs and in addition to suggest measures to reduce the abuse of substances and drugs...
October 20, 2017: Current Drug Abuse Reviews
https://www.readbyqxmd.com/read/29063964/phytocannabinoids-modulate-emotional-memory-processing-through-interactions-with-the-ventral-hippocampus-and-mesolimbic-dopamine-system-implications-for-neuropsychiatric-pathology
#3
REVIEW
Roger Hudson, Walter Rushlow, Steven R Laviolette
Growing clinical and preclinical evidence suggests a potential role for the phytocannabinoid cannabidiol (CBD) as a pharmacotherapy for various neuropsychiatric disorders. In contrast, delta-9-tetrahydrocannabinol (THC), the primary psychoactive component in cannabis, is associated with acute and neurodevelopmental propsychotic side effects through its interaction with central cannabinoid type 1 receptors (CB1Rs). CB1R stimulation in the ventral hippocampus (VHipp) potentiates affective memory formation through inputs to the mesolimbic dopamine (DA) system, thereby altering emotional salience attribution...
October 24, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/29046483/deficiency-of-shank2-causes-mania-like-behavior-that-responds-to-mood-stabilizers
#4
Andrea L Pappas, Alexandra L Bey, Xiaoming Wang, Mark Rossi, Yong Ho Kim, Haidun Yan, Fiona Porkka, Lara J Duffney, Samantha M Phillips, Xinyu Cao, Jin-Dong Ding, Ramona M Rodriguiz, Henry H Yin, Richard J Weinberg, Ru-Rong Ji, William C Wetsel, Yong-Hui Jiang
Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly understood. We generated and characterized a line of Shank2 mutant mice by deleting exon 24 (Δe24). Shank2Δe24-/- mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/28965780/drug-related-predictors-of-readmission-for-schizophrenia-among-patients-admitted-to-treatment-for-drug-use-disorders
#5
Kristine Rømer Thomsen, Birgitte Thylstrup, Michael Mulbjerg Pedersen, Mads Uffe Pedersen, Erik Simonsen, Morten Hesse
BACKGROUND: Patients with schizophrenia and comorbid drug use disorders (DUD) have a severe course of illness. Despite strong evidence that drug use can exacerbate psychotic symptoms, we have limited knowledge of how specific drugs may increase risk of schizophrenia readmission in this group. This study aimed to assess drug-related predictors of readmission for schizophrenia among a national cohort of patients with a history of schizophrenia admitted to DUD treatment. METHODS: A record-linkage study was used to assess drug-related factors associated with readmission to mental health treatment for schizophrenia, using a consecutive cohort of 634 patients admitted to DUD treatment between 2000 and 2006 in Danish treatment services and tracked until February 2013 or death, controlling for baseline psychiatric treatment variables...
September 28, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28927551/impaired-contextual-fear-conditioning-in-mam-rodent-model-of-schizophrenia
#6
Kathryn M Gill, Sarah A Miller, Anthony A Grace
The methylazoxymethanol acetate (MAM) rodent neurodevelopmental model of schizophrenia exhibits aberrant dopamine system activation attributed to hippocampal dysfunction. Context discrimination is a component of numerous behavioral and cognitive functions and relies on intact hippocampal processing. The present study explored context processing behaviors, along with dopamine system activation, during fear learning in the MAM model. Male offspring of dams treated with MAM (20mg/kg, i.p.) or saline on gestational day 17 were used for electrophysiological and behavioral experiments...
September 15, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28700108/gpr88-in-a2a-receptor-expressing-neurons-modulates-locomotor-response-to-dopamine-agonists-but-not-sensorimotor-gating
#7
A C Meirsman, A de Kerchove d'Exaerde, B L Kieffer, A-M Ouagazzal
The orphan receptor, GPR88, is emerging as a key player in the pathophysiology of several neuropsychiatric diseases, including psychotic disorders. Knockout (KO) mice lacking GPR88 throughout the brain exhibit many abnormalities relevant to schizophrenia including locomotor hyperactivity, behavioural hypersensitivity to dopaminergic psychostimulants and deficient sensorimotor gating. Here, we used conditional knockout (cKO) mice lacking GPR88 selectively in striatal medium spiny neurons expressing A2A receptor to determine neuronal circuits underlying these phenotypes...
August 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28674745/selective-enhancement-of-nmda-receptor-mediated-locomotor-hyperactivity-by-male-sex-hormones-in-mice
#8
Maarten van den Buuse, Jac Kee Low, Perrin Kwek, Sally Martin, Andrea Gogos
RATIONALE: Altered glutamate NMDA receptor function is implicated in schizophrenia, and gender differences have been demonstrated in this illness. OBJECTIVES: This study aimed to investigate the interaction of gonadal hormones with NMDA receptor-mediated locomotor hyperactivity and PPI disruption in mice. RESULTS: The effect of 0.25 mg/kg of MK-801 on locomotor activity was greater in male mice than in female mice. Gonadectomy (by surgical castration) significantly reduced MK-801-induced hyperlocomotion in male mice, but no effect of gonadectomy was seen in female mice or on amphetamine-induced locomotor hyperactivity...
July 3, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28634445/antioxidant-treatment-with-n-acetyl-cysteine-prevents-the-development-of-cognitive-and-social-behavioral-deficits-that-result-from-perinatal-ketamine-treatment
#9
Aarron Phensy, Hasmik E Duzdabanian, Samantha Brewer, Anurag Panjabi, Christopher Driskill, Annuska Berz, George Peng, Sven Kroener
Alterations of the normal redox state can be found in all stages of schizophrenia, suggesting a key role for oxidative stress in the etiology and maintenance of the disease. Pharmacological blockade of N-methyl-D-aspartic acid (NMDA) receptors can disrupt natural antioxidant defense systems and induce schizophrenia-like behaviors in animals and healthy human subjects. Perinatal administration of the NMDA receptor (NMDAR) antagonist ketamine produces persistent behavioral deficits in adult mice which mimic a range of positive, negative, and cognitive symptoms that characterize schizophrenia...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28634087/treatment-with-levetiracetam-improves-cognition-in-a-ketamine-rat-model-of-schizophrenia
#10
Ming Teng Koh, Yi Shao, Sharon Rosenzweig-Lipson, Michela Gallagher
Imbalance in neural excitation and inhibition is associated with behavioral dysfunction in individuals with schizophrenia and at risk for this illness. We examined whether targeting increased neural activity with the antiepileptic agent, levetiracetam, would benefit memory performance in a preclinical model of schizophrenia that has been shown to exhibit hyperactivity in the hippocampus. Adult rats exposed to ketamine subchronically during late adolescence showed impaired hippocampal-dependent memory performance...
June 17, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28579351/preclinical-abuse-liability-assessment-of-abt-126-an-agonist-at-the-%C3%AE-7-nicotinic-acetylcholine-receptor-nachr
#11
Thomas J Hudzik, Ana M Basso, James J Lynch, William M Bracken, Eric G Mohler, Kathy L Kohlhaas, Hongyu Xu, George Haig, Laura Gault
ABT-126 is a nicotinic acetylcholine receptor (nAChR) agonist that is selective for the α7 subtype of the receptor. nAChRs are thought to play a role in a variety of neurocognitive processes and have been a pharmacologic target for disorders with cognitive impairment, including schizophrenia and Alzheimer's disease. As part of the preclinical safety package for ABT-126, its potential for abuse was assessed. While the involvement of the α4β2 subtype of the nicotinic receptor in the addictive properties of nicotine has been demonstrated, the role of the α7 receptor has been studied much less extensively...
July 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28507321/pet-imaging-of-dopamine-d2-receptor-internalization-in-schizophrenia
#12
J J Weinstein, E van de Giessen, R J Rosengard, X Xu, N Ojeil, G Brucato, R B Gil, L S Kegeles, M Laruelle, M Slifstein, A Abi-Dargham
Recent genetic, molecular and post-mortem studies suggest impaired dopamine (DA)-D2 receptor (D2R) trafficking in patients with schizophrenia (SZ). Imaging and preclinical studies have shown agonist-induced D2R internalization can be imaged with positron emission tomography (PET) using D2R radiotracers combined with psychostimulant challenge. This is feasible if radiotracer binding is measured when postchallenge DA levels have returned to baseline, following the initial competition phase between DA and radiotracer for binding to D2R...
May 16, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28454982/dopamine-transporter-dat-genetic-hypofunction-in-mice-produces-alterations-consistent-with-adhd-but-not-schizophrenia-or-bipolar-disorder
#13
M Mereu, G Contarini, E F Buonaguro, G Latte, F Managò, F Iasevoli, A de Bartolomeis, F Papaleo
ADHD, schizophrenia and bipolar disorder are psychiatric diseases with a strong genetic component which share dopaminergic alterations. Dopamine transporter (DAT) genetics might be potentially implicated in all these disorders. However, in contrast to DAT absence, the effects of DAT hypofunction especially in developmental trajectories have been scarcely addressed. Thus, we comprehensively studied DAT hypofunctional mice (DAT+/-) from adolescence to adulthood to disentangle DAT-dependent alterations in the development of psychiatric-relevant phenotypes...
July 15, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28433741/loss-of-the-neurodevelopmental-gene-zswim6-alters-striatal-morphology-and-motor-regulation
#14
David J Tischfield, Dave K Saraswat, Andrew Furash, Stephen C Fowler, Marc V Fuccillo, Stewart A Anderson
The zinc-finger SWIM domain-containing protein 6 (ZSWIM6) is a protein of unknown function that has been associated with schizophrenia and limited educational attainment by three independent genome-wide association studies. Additionally, a putatively causal point mutation in ZSWIM6 has been identified in several cases of acromelic frontonasal dysostosis with severe intellectual disability. Despite the growing number of studies implicating ZSWIM6 as an important regulator of brain development, its role in this process has never been examined...
July 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28421658/transcriptional-signatures-of-connectomic-subregions-of-the-human-striatum
#15
L Parkes, B D Fulcher, M Yücel, A Fornito
Functionally distinct regions of the brain are thought to possess a characteristic connectional fingerprint - a profile of incoming and outgoing connections that defines the function of that area. This observation has motivated efforts to subdivide brain areas using their connectivity patterns. However, it remains unclear whether these connectomically-defined subregions can be distinguished at the molecular level. Here, we combine high-resolution diffusion-weighted magnetic resonance imaging with transcriptomic data to show that connectomically-defined subregions of the striatum carry distinct transcriptional signatures...
April 19, 2017: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/28390877/effects-of-chronic-prenatal-mk-801-treatment-on-object-recognition-cognitive-flexibility-and-drug-induced-locomotor-activity-in-juvenile-and-adult-rat-offspring
#16
S Gallant, L Welch, P Martone, U Shalev
BACKGROUND: Patients with schizophrenia display impaired cognitive functioning and increased sensitivity to psychomimetic drugs. The neurodevelopmental hypothesis of schizophrenia posits that disruption of the developing brain predisposes neural networks to lasting structural and functional abnormalities resulting in the emergence of such symptoms in adulthood. Given the critical role of the glutamatergic system in early brain development, we investigated whether chronic prenatal exposure to the glutamate NMDA receptor antagonist, MK-801, induces schizophrenia-like behavioural and neurochemical changes in juvenile and adult rats...
April 6, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28377698/striatal-cholinergic-interneurons-modulate-spike-timing-in-striosomes-and-matrix-by-an-amphetamine-sensitive-mechanism
#17
Jill R Crittenden, Carolyn J Lacey, Feng-Ju Weng, Catherine E Garrison, Daniel J Gibson, Yingxi Lin, Ann M Graybiel
The striatum is key for action-selection and the motivation to move. Dopamine and acetylcholine release sites are enriched in the striatum and are cross-regulated, possibly to achieve optimal behavior. Drugs of abuse, which promote abnormally high dopamine release, disrupt normal action-selection and drive restricted, repetitive behaviors (stereotypies). Stereotypies occur in a variety of disorders including obsessive-compulsive disorder, autism, schizophrenia and Huntington's disease, as well as in addictive states...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/28373127/rp5063-an-atypical-antipsychotic-drug-with-a-unique-pharmacologic-profile-improves-declarative-memory-and-psychosis-in-mouse-models-of-schizophrenia
#18
Lakshmi Rajagopal, Sunoh Kwon, Mei Huang, Eric Michael, Laxminarayan Bhat, Marc Cantillon, Herbert Y Meltzer
Various types of atypical antipsychotic drugs (AAPDs) modestly improve the cognitive impairment associated with schizophrenia (CIAS). RP5063 is an AAPD with a diverse and unique pharmacology, including partial agonism at dopamine (DA) D2, D3, D4, serotonin (5-HT)1A, and 5-HT2A receptors (Rs), full agonism at α4β2 nicotinic acetylcholine (ACh)R (nAChR), and antagonism at 5-HT2B, 5-HT6, and 5-HT7Rs. Most atypical APDs are 5-HT2A inverse agonists. The efficacy of RP5063 in mouse models of psychosis and episodic memory were studied...
March 31, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28365388/comparative-analysis-of-mbd-seq-and-medip-seq-and-estimation-of-gene-expression-changes-in-a-rodent-model-of-schizophrenia
#19
COMPARATIVE STUDY
Jennifer L Neary, Stephanie M Perez, Kara Peterson, Daniel J Lodge, Melanie A Carless
We conducted a comparative study of multiplexed affinity enrichment sequence methodologies (MBD-seq and MeDIP-seq) in a rodent model of schizophrenia, induced by in utero methylazoxymethanol acetate (MAM) exposure. We also examined related gene expression changes using a pooled sample approach. MBD-seq and MeDIP-seq identified 769 and 1771 differentially methylated regions (DMRs) between F2 offspring of MAM-exposed rats and saline control rats, respectively. The assays showed good concordance, with ~56% of MBD-seq-detected DMRs being identified by or proximal to MeDIP-seq DMRs...
July 2017: Genomics
https://www.readbyqxmd.com/read/28322273/neuregulin-2-ablation-results-in-dopamine-dysregulation-and-severe-behavioral-phenotypes-relevant-to-psychiatric-disorders
#20
L Yan, A Shamir, M Skirzewski, E Leiva-Salcedo, O B Kwon, I Karavanova, D Paredes, O Malkesman, K R Bailey, D Vullhorst, J N Crawley, A Buonanno
Numerous genetic and functional studies implicate variants of Neuregulin-1 (NRG1) and its neuronal receptor ErbB4 in schizophrenia and many of its endophenotypes. Although the neurophysiological and behavioral phenotypes of NRG1 mutant mice have been investigated extensively, practically nothing is known about the function of NRG2, the closest NRG1 homolog. We found that NRG2 expression in the adult rodent brain does not overlap with NRG1 and is more extensive than originally reported, including expression in the striatum and medial prefrontal cortex (mPFC), and therefore generated NRG2 knockout mice (KO) to study its function...
March 21, 2017: Molecular Psychiatry
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