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https://www.readbyqxmd.com/read/29329382/adolescent-synthetic-cannabinoid-exposure-produces-enduring-changes-in-dopamine-neuron-activity-in-a-rodent-model-of-schizophrenia-susceptibility
#1
David D Aguilar, Andrea Giuffrida, Daniel J Lodge
Background: Epidemiological studies recognize cannabis intake as a risk factor for schizophrenia, yet the majority of adolescents who use marijuana do not develop psychosis. Similarly, the abuse of synthetic cannabinoids poses a risk for psychosis. For these reasons, it is imperative to understand the effects of adolescent cannabinoid exposure in susceptible individuals. Method: We have recently developed a novel rodent model of schizophrenia susceptibility, the F2 MAM rat, where only a proportion (~40%) of rats display a schizophrenia-like phenotype...
January 10, 2018: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29326171/abdominal-vagal-afferents-modulate-the-brain-transcriptome-and-behaviors-relevant-to-schizophrenia
#2
Melanie Klarer, Jean-Philippe Krieger, Juliet Richetto, Ulrike Weber-Stadlbauer, Lydia Günther, Christine Winter, Myrtha Arnold, Wolfgang Langhans, Urs Meyer
Reduced activity of vagal efferents has long been implicated in schizophrenia and appears to be responsible for diminished parasympathetic activity and associated peripheral symptoms such as low heart rate variability and cardiovascular complications in affected individuals. In contrast, only little attention has been paid to the possibility that impaired afferent vagal signaling may be relevant for the disorder's pathophysiology as well. The present study explored this hypothesis using a model of subdiaphragmatic vagal deafferentation (SDA) in male rats...
January 11, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29325847/amphetamine-induced-striatal-dopamine-release-measured-with-an-agonist-radiotracer-in%C3%A2-schizophrenia
#3
W Gordon Frankle, Jennifer Paris, Michael Himes, N Scott Mason, Chester A Mathis, Rajesh Narendran
BACKGROUND: Receptor imaging studies have reported increased amphetamine-induced dopamine release in subjects with schizophrenia (SCH) relative to healthy control subjects (HCs). A limitation of these studies, performed with D2/3 antagonist radiotracers, is the failure to provide information about D2/3 receptors configured in a state of high affinity for the agonists (i.e., D2/3 receptors coupled to G proteins [D2/3 HIGH]). The endogenous agonist dopamine binds with preference to D2/3 HIGH receptors relative to D2/3 LOW receptors, making it critical to understand the status of D2/3 HIGH receptors in SCH...
December 7, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/29275180/effect-of-clozapine-dose-and-concentration-on-fasting-concentration-of-appetite-regulating-peptides
#4
Aleksandra Margulska, Elżbieta Kozłowska, Adam Wysokiński
The aim of this study is to analyze whether clozapine serum concentration may affect fasting serum levels of several appetite regulating peptides: CART, PYY(1-36), NPY, AgRP, des-acylated ghrelin, leptin and obestatin. Serum concentration of clozapine and fasting serum levels of des-acylated ghrelin, neuropeptide Y (NPY), agouti-related protein (AgRP), peptide YY (PYY(1-36)), cocaine- and amphetamine-regulated transcript (CART), leptin and obestatin were measured in 30 subjects with schizophrenia on clozapine monotherapy...
December 10, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/29249806/cortical-high-gamma-network-oscillations-and-connectivity-a-translational-index-for-antipsychotics-to-normalize-aberrant-neurophysiological-activity
#5
A Ahnaou, H Huysmans, T Van de Casteele, W H I M Drinkenburg
Oscillatory activity in the gamma frequency range is a critical mechanism, which integrates neural networks within and across brain structures during cognitive processes. In schizophrenia, abnormalities in high gamma oscillations are ubiquitous and most likely reflect dysfunction in neuronal networks. In conscious rats, disturbed network oscillations associated with positive symptoms and cognitive deficits were modeled in different cortical areas by the dopaminergic agonist (amphetamine) and the N-methyl-D-aspartate (NMDA) receptor antagonists (PCP and MK801)...
December 18, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29236922/effects-of-n-acetylcysteine-on-amphetamine-induced-sensitization-in-mice
#6
Ana P Herrmann, Roberta Andrejew, Radharani Benvenutti, Clarissa S Gama, Elaine Elisabetsky
OBJECTIVE: N-acetylcysteine (NAC) is beneficial in psychiatric conditions, including schizophrenia. Patients with schizophrenia exhibit mesolimbic dopamine hyperfunction consequent to an endogenous sensitization process. This sensitization can be modeled in rodents by repeated exposure to psychostimulants, provoking an enduring amplified response at subsequent exposure. The aim of this study was to investigate the effects of NAC on amphetamine sensitization in mice. METHODS: D-amphetamine was administered to C57BL/6 mice three times a week for 3 weeks; the dose was increased weekly from 1 to 3 mg/kg...
December 11, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/29195684/mice-lacking-interleukin-18-gene-display-behavioral-changes-in-animal-models-of-psychiatric-disorders-possible-involvement-of-immunological-mechanisms
#7
S F Lisboa, A C Issy, C Biojone, K Montezuma, V Fattori, E A Del-Bel, F S Guimarães, F Q Cunha, W A Verri, S R L Joca
Preclinical and clinical evidence suggests pro-inflammatory cytokines might play an important role in the neurobiology of schizophrenia and stress-related psychiatric disorders. Interleukin-18 (IL-18) is a member of the IL-1 family of cytokines and it is widely expressed in brain regions involved in emotional regulation. Since IL-18 involvement in the neurobiology of mental illnesses, including schizophrenia, remains unknown, this work aimed at investigating the behavior of IL-18 null mice (KO) in different preclinical models: 1...
November 10, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29187755/a-mouse-model-of-the-schizophrenia-associated-1q21-1-microdeletion-syndrome-exhibits-altered-mesolimbic-dopamine-transmission
#8
Jacob Nielsen, Kim Fejgin, Florence Sotty, Vibeke Nielsen, Arne Mørk, Claus T Christoffersen, Leonid Yavich, Jes B Lauridsen, Dorte Clausen, Peter H Larsen, Jan Egebjerg, Thomas M Werge, Pekka Kallunki, Kenneth V Christensen, Michael Didriksen
1q21.1 hemizygous microdeletion is a copy number variant leading to eightfold increased risk of schizophrenia. In order to investigate biological alterations induced by this microdeletion, we generated a novel mouse model (Df(h1q21)/+) and characterized it in a broad test battery focusing on schizophrenia-related assays. Df(h1q21)/+ mice displayed increased hyperactivity in response to amphetamine challenge and increased sensitivity to the disruptive effects of amphetamine and phencyclidine hydrochloride (PCP) on prepulse inhibition...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29154367/effects-of-amphetamine-on-sensorimotor-gating-and-neurocognition-in-antipsychotic-medicated-schizophrenia-patients
#9
Neal R Swerdlow, Savita G Bhakta, Jo A Talledo, Daniel M Franz, Erica L Hughes, Brinda K Rana, Gregory A Light
Prepulse inhibition (PPI) of startle is being explored both as an indicator of target engagement for, and a biomarker predicting sensitivity to, pro-cognitive effects of drugs. We now report the effects of the pro-attentional drug, d-amphetamine, on PPI and neurocognition in antipsychotic-medicated schizophrenia patients and healthy subjects (HS) who were also tested in a targeted cognitive training (TCT) module. 44 HS and 38 schizophrenia patients completed a double-blind, placebo-controlled crossover study of the effects of a single dose of amphetamine (10 mg po) on PPI and MATRICS Consensus Cognitive Battery (MCCB) performance; TCT results were previously reported from 60 of these subjects...
November 20, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29116599/the-class-a-gpcr-dopamine-d2-receptor-forms-transient-dimers-stabilized-by-agonists-detection-by-single-molecule-tracking
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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