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https://www.readbyqxmd.com/read/28226265/alterations-of-ubiquitin-related-proteins-in-the-pathology-and-development-of-schizophrenia-evidence-from-human-and-animal-studies
#1
Jessica L Andrews, Frederic J Goodfellow, Natalie Matosin, Mollie K Snelling, Kelly A Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia...
January 18, 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28167638/effects-of-repeated-ropinirole-treatment-on-phencyclidine-induced-hyperlocomotion-prepulse-inhibition-deficits-and-social-avoidance-in-rats
#2
Amanda M Maple, Tanessa Call, Phylicia C Kimmel, Ronald P Hammer
Phencyclidine (PCP), a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, provides the most complete pharmacological model of schizophrenia in humans and animals. Acute PCP causes hyperlocomotion, disrupts prepulse inhibition (PPI), and increases social avoidance in rats. We previously showed that repeated treatment with the dopamine (DA) D2-like receptor agonists, quinpirole or ropinirole, prevents agonist-induced PPI disruption. The present study examines whether repeated ropinirole treatment similarly attenuates the effects of PCP in a more complete model of schizophrenia symptoms...
February 6, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28167336/trans-generation-enrichment-of-clozapine-responsiveness-trait-in-mice-using-a-subchronic-hypo-glutamatergic-model-of-schizophrenia-a-preliminary-study
#3
Amir Krivoy, Irit Gil-Ad, Igor Tarasenko, Abraham Weizman, Michal Taler
BACKGROUND: Schizophrenia patients who do not respond to clozapine treatment represent the most debilitating type of schizophrenia with unmet needs for novel interventions. To date there is no validated animal model for clozapine-refractory schizophrenia. METHODS: We used poor performance in the social preference (SP) test of C57/BL mice exposed to subchronic phencyclidine (PCP) as a correlate of negative signs of schizophrenia. Subsequently the mice were treated with clozapine and according to their SP they were defined as responding (i...
February 3, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28158698/two-cases-of-non-fatal-intoxication-with-a-novel-street-hallucinogen-3-methoxy-phencyclidine
#4
Monika Zidkova, Tomas Hlozek, Martin Balik, Ondrej Kopecky, Pavel Tesinsky, Jan Svanda, Marie Anna Balikova
No abstract text is available yet for this article.
February 2, 2017: Journal of Analytical Toxicology
https://www.readbyqxmd.com/read/28121123/n-methyl-d-aspartate-modulation-of-nucleus-accumbens-dopamine-release-by-metabotropic-glutamate-receptors-fast-cyclic-voltammetry-studies-in-rat-brain-slices-in-vitro
#5
Ersin Yavas, Andrew M J Young
The N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine, induces behavioral changes in rodents mimicking symptoms of schizophrenia, possibly mediated through dysregulation of glutamatergic control of mesolimbic dopamine release. We tested the hypothesis that NMDA receptor activation modulates accumbens dopamine release, and that phencyclidine pretreatment altered this modulation. NMDA caused a receptor-specific, dose-dependent decrease in electrically stimulated dopamine release in nucleus accumbens brain slices...
February 1, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28119266/drugs-in-hair-part-i-metabolisms-of-major-drug-classes
#6
REVIEW
R M White
Currently, hair can be reliably tested for the presence of drugs. However, one major drawback to the use of parent drugs is the question of potential external or environmental contamination. The analysis of metabolites to confirm the use of the parent drugs was proposed in this short review. The development of hair as a test matrix and the incorporation of xenobiotics, in general, into the hair matrix were discussed. What constitutes an appropriate metabolite for drug testing to mirror the use of a parent drug was proposed and discussed...
January 2017: Forensic Science Review
https://www.readbyqxmd.com/read/28111261/sex-differences-in-psychotomimetic-induced-behaviours-in-rats
#7
Andrea Gogos, Snezana Kusljic, Shane J Thwaites, Maarten van den Buuse
Animal model studies using equal numbers of males and females are sparse in psychiatry research. Given the marked sex differences observed in psychiatric disorders, such as schizophrenia, using both males and females in research studies is an important requirement. Thus the aim of this study was to examine sex differences in psychotomimetic-induced behavioural deficits relevant to psychosis. We therefore compared the acute effect of amphetamine or phencyclidine on locomotor activity and prepulse inhibition in adult male and female Sprague-Dawley rats...
January 19, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28087359/the-effect-of-nmda-r-antagonism-on-simultaneously-acquired-local-field-potentials-and-tissue-oxygen-levels-in-the-brains-of-freely-moving-rats
#8
John Kealy, Sean Commins, John P Lowry
Non-competitive NMDA receptor antagonists are known to induce psychosis-like symptoms in rodents. Administration of such compounds cause behavioural effects such as memory impairment and hyperlocomotion. Additionally, drugs such as phencyclidine (PCP), ketamine and MK-801 all cause distinctive increases in striatal local field potential (LFP) in the high frequency oscillation (HFO) band in the power spectrum (140-180 Hz). Amperometric sensors provide a means to measure tissue oxygen (tO2; a BOLD-like signal) in the brains of freely-moving rats while simultaneously acquiring LFP using the same electrode...
January 11, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28057371/3-meo-pcp-intoxication-in-two-young-men-first-in-vivo-detection-in-italy
#9
Elisabetta Bertol, Jennifer Pascali, Diego Palumbo, Valeria Catalani, Maria Grazia Di Milia, Alessia Fioravanti, Francesco Mari, Fabio Vaiano
3-MeO-PCP or 3-methoxyphencyclidine is a derivative of phencyclidine. It acts as a dissociative anesthetic and it has allegedly hallucinogenic and sedative effects. There are almost no documented intoxication cases and references about its pharmacology and toxicity in literature. This study presents two concomitant intoxication cases due to consumption of 3-MeO-PCP and alcohol. A 19 (A) and a 21 years old (B) men were brought to Santa Maria Nuova Hospital in a comatose state (Glasgow score 3). They showed respiratory acidosis, right anisocoria with mydriatic pupils and hypothermia...
December 26, 2016: Forensic Science International
https://www.readbyqxmd.com/read/28031399/neurons-derived-from-different-brain-regions-are-inherently-different-in-vitro-a-novel-multiregional-brain-on-a-chip
#10
Stephanie Dauth, Ben M Maoz, Sean P Sheehy, Matthew A Hemphill, Tara Murty, Mary Kate Macedonia, Angie M Greer, Bogdan Budnik, Kevin Kit Parker
Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: The scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro...
December 28, 2016: Journal of Neurophysiology
https://www.readbyqxmd.com/read/27986516/effects-of-withdrawal-from-repeated-phencyclidine-administration-on-behavioural-function-and-brain-arginine-metabolism-in-rats
#11
Logan T Knox, Yu Jing, Jamal Bawazier-Edgecombe, Nicola D Collie, Hu Zhang, Ping Liu
Phencyclidine (PCP) induces behavioural changes in humans and laboratory animals that resemble positive and negative symptoms, and cognitive impairments in schizophrenia. It has been shown repeated treatment of PCP leading to persistent symptoms even after the drug discontinuation, and there is a growing body of evidence implicating altered arginine metabolism in the pathogenesis of schizophrenia. The present study investigated the effects of withdrawal from repeated daily injection of PCP (2mg/kg) for 12 consecutive days on animals'behavioural performance and arginine metabolism in the hippocampus and prefrontal cortex in male young adult rats...
February 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/27986355/the-prolyl-oligopeptidase-inhibitor-ipr19-ameliorates-cognitive-deficits-in-mouse-models-of-schizophrenia
#12
Roger Prades, Eva Munarriz-Cuezva, Leyre Urigüen, Itziar Gil-Pisa, Lídia Gómez, Laura Mendieta, Soledad Royo, Ernest Giralt, Teresa Tarragó, J Javier Meana
Cognitive deficits are considered a key feature of schizophrenia, and they usually precede the onset of the illness and continue after psychotic symptoms appear. Current antipsychotic drugs have little or no effect on the cognitive deficits of this disorder. Prolyl oligopeptidase (POP) is an 81-kDa monomeric serine protease that is expressed in brain and other tissues. POP inhibitors have shown neuroprotective, anti-amnesic and cognition-enhancing properties. Here we studied the potential of IPR19, a new POP inhibitor, for the treatment of the cognitive symptoms related to schizophrenia...
February 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27916716/effects-of-a-non-competitive-n-methyl-d-aspartate-nmda-antagonist-tiletamine-in-adult-zebrafish
#13
Tatiana O Kolesnikova, Sergey L Khatsko, Vadim A Shevyrin, Yuri Yu Morzherin, Allan V Kalueff
Tiletamine is a non-competitive N-methyl-d-aspartate (NMDA) receptor antagonist chemically related to ketamine and phencyclidine. A common veterinary anesthetic drug, tiletamine is currently a Schedule III controlled substance in USA. This compound exerts sedative effects in humans and animals, also having an abuse potential, toxicity and dissociative hallucinogenic properties clinically. However, the neurotropic profile of tiletamine remains poorly understood, necessitating novel models and in-vivo screens, including non-mammalian species...
December 2, 2016: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27822508/clozapine-n-oxide-administration-produces-behavioral-effects-in-long-evans-rats-implications-for-designing-dreadd-experiments
#14
Duncan A A MacLaren, Richard W Browne, Jessica K Shaw, Sandhya Krishnan Radhakrishnan, Prachi Khare, Rodrigo A España, Stewart D Clark
Clozapine N-oxide (CNO) is a ligand for a powerful chemogenetic system that can selectively inhibit or activate neurons; the so-called Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system. This system consists of synthetic G-protein-coupled receptors, which are not believed to be activated by any endogenous ligand, but are activated by the otherwise inert CNO. However, it has previously been shown that the administration of CNO in humans and rats leads to detectable levels of the bioactive compounds clozapine and N-desmethylclozapine (N-Des)...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27796745/protective-potential-of-the-glutathione-peroxidase-1-gene-in-abnormal-behaviors-induced-by-phencyclidine-in-mice
#15
The-Vinh Tran, Eun-Joo Shin, Ji Hoon Jeong, Ji Won Lee, Youngho Lee, Choon-Gon Jang, Seung-Yeol Nah, Xin Gen Lei, Kazuya Toriumi, Kiyofumi Yamada, Toshitaka Nabeshima, Hyoung-Chun Kim
Escalating evidence suggests that the impairment of glutathione (GSH)-dependent systems is one of the etiologic factors of schizophrenia. GSH is an important substrate of glutathione peroxidase (GPx). Among GPx isozymes, selenium-dependent GPx (GPx-1) is recognized as a major type, and therefore, this study investigates the role of the GPx-1 gene in abnormal behaviors induced by repeated phencyclidine (PCP) treatment using GPx-1 knockout (KO) and overexpressing transgenic (GPx-1 TG) mice. PCP-induced abnormal behaviors were more pronounced in GPx-1 KO mice than abnormal behaviors in wild-type (WT) mice, and the abnormal behaviors were less pronounced in GPx-1 TG mice than abnormal behaviors in non-TG mice...
October 28, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27721531/are-therapeutic-vaccines-an-answer-to-the-global-problem-of-drug-and-alcohol-abuse
#16
Dick B S Brashier, Ashok Kumar Sharma, Neha Akhoon
Drug Abuse has become a major challenging problem for the society. It effects people of all countries economical strata's and all ages. According. Monetary loss all over the world regarding drug abuse is in million dollars, it not only has an impact on human productivity and healthcare cost but also on cost of crimes conducted by these drugs and alcohol abuse. Therapeutic vaccine has come as new approach to deal with this problem, after failures in search for a pharmaceutical agent to deal with drug of abuse and alcohol...
September 2016: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/27721389/neurodevelopmental-expression-profile-of-dimeric-and-monomeric-group-1-mglurs-relevance-to-schizophrenia-pathogenesis-and-treatment
#17
Jeremy S Lum, Francesca Fernandez, Natalie Matosin, Jessica L Andrews, Xu-Feng Huang, Lezanne Ooi, Kelly A Newell
Group 1 metabotropic glutamate receptors (mGluR1/mGluR5) play an integral role in neurodevelopment and are implicated in psychiatric disorders, such as schizophrenia. mGluR1 and mGluR5 are expressed as homodimers, which is important for their functionality and pharmacology. We examined the protein expression of dimeric and monomeric mGluR1α and mGluR5 in the prefrontal cortex (PFC) and hippocampus throughout development (juvenile/adolescence/adulthood) and in the perinatal phencyclidine (PCP) model of schizophrenia...
October 10, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27668757/mountain-cultivated-ginseng-attenuates-phencyclidine-induced-abnormal-behaviors-in-mice-by-positive-modulation-of-glutathione-in-the-prefrontal-cortex-of-mice
#18
The-Vinh Tran, Eun-Joo Shin, Sung Kwon Ko, Yunsung Nam, Yoon Hee Chung, Ji Hoon Jeong, Choon-Gon Jang, Seung-Yeol Nah, Kiyofumi Yamada, Toshitaka Nabeshima, Jae Kyung Byun, Hyoung-Chun Kim
Escalating evidence indicates that ginseng treatment protects against psychotoxic behaviors and memory impairment. Although the underlying mechanism of schizophrenia remains elusive, recent investigations proposed that downregulation of glutathione (GSH) can be involved in the pathogenesis of this disorder. Since little is known about the effects of ginseng in a schizophrenia-like animal model, we selected mountain-cultivated ginseng (MG) from a variety of ginseng extracts to investigate the effect of ginseng on the psychosis induced by phencyclidine (PCP) in mice...
September 26, 2016: Journal of Medicinal Food
https://www.readbyqxmd.com/read/27665567/new-psychoactive-substances-an-overview-on-recent-publications-on-their-toxicodynamics-and-toxicokinetics
#19
REVIEW
Markus R Meyer
This review article covers English-written and PubMed-listed review articles and original studies published between January 2015 and April 2016 dealing with the toxicodynamics and toxicokinetics of new psychoactive substances. Compounds covered include stimulants and entactogens, synthetic cannabinoids, tryptamines, NBOMes, phencyclidine-like drugs, benzodiazepines, and opioids. First, an overview and discussion is provided on timely review articles followed by an overview and discussion on recent original studies...
October 2016: Archives of Toxicology
https://www.readbyqxmd.com/read/27624147/modelling-the-cognitive-and-neuropathological-features-of-schizophrenia-with-phencyclidine
#20
Gavin P Reynolds, Joanna C Neill
Here, Reynolds and Neill describe the studies that preceded and followed publication of this paper, which reported a deficit in parvalbumin (PV), a calcium-binding protein found in GABA interneurons known to be reduced in schizophrenia patients, in conjunction with a deficit in reversal learning in an animal model for schizophrenia. This publication resulted from common research interests: Reynolds in the neurotransmitter pathology of schizophrenia, and Neill in developing animal models for schizophrenia symptomatology...
September 13, 2016: Journal of Psychopharmacology
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