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Schizophrenia amphetamine

Rebecca McKetin
BACKGROUND AND AIMS: To review early case reports and experimental inductions of amphetamine and methamphetamine psychosis, prior to the prohibition of these drugs, to gain a better understanding of the nature and aetiology of methamphetamine psychosis. METHODS: Papers considered were historical case reports and case series of psychosis relating to the use and misuse of prescription amphetamine, focusing upon papers by Young & Scoville (1938), Connell (1958), and three subsequent experimental studies published in the early 1970s (Griffith 1972, Angrist & Gershon 1970 and Bell 1973), where psychosis was induced in volunteers using high-dose amphetamine and methamphetamine...
March 8, 2018: Addiction
Michel Weïwer, Qihong Xu, Jennifer P Gale, Michael Lewis, Arthur J Campbell, Frederick A Schroeder, Genevieve C Van de Bittner, Michelle Walk, Aldo Amaya, Ping Su, Luka D Ordevic, Joshua R Sacher, Adam Skepner, David Fei, Kelly Dennehy, Shannon Nguyen, Patrick W Faloon, Jose Perez, Jeffrey R Cottrell, Fang Liu, Michelle Palmer, Jen Q Pan, Jacob M Hooker, Yan-Ling Zhang, Edward Scolnick, Florence F Wagner, Edward B Holson
Schizophrenia is a severe neuropsychiatric disease that lacks completely effective and safe therapies. As a polygenic disorder, genetic studies have only started to shed light on its complex etiology. To date, the positive symptoms of schizophrenia are well-managed by antipsychotic drugs, which primarily target the dopamine D2 receptor (D2R). However, these antipsychotics are often accompanied by severe side effects, including motoric symptoms. At D2R, antipsychotic drugs antagonize both G-protein dependent (Gαi/o ) signaling and G-protein independent (β-arrestin) signaling...
March 14, 2018: ACS Chemical Biology
Sharon S Lander, Usman Khan, Nicole Lewandowski, Darpan Chakraborty, Frank A Provenzano, Susana Mingote, Sergiy Chornyy, Francesca Frigerio, Pierre Maechler, Hanoch Kaphzan, Scott A Small, Stephen Rayport, Inna Gaisler-Salomon
Brain imaging has revealed that the CA1 subregion of the hippocampus is hyperactive in prodromal and diagnosed patients with schizophrenia (SCZ), and that glutamate is a driver of this hyperactivity. Strikingly, mice deficient in the glutamate synthetic enzyme glutaminase have CA1 hypoactivity and a SCZ-resilience profile, implicating glutamate-metabolizing enzymes. To address this further, we examined mice with a brain-wide deficit in the glutamate-metabolizing enzyme glutamate dehydrogenase (GDH), encoded by Glud1, which should lead to glutamate excess due to reduced glutamate metabolism in astrocytes...
February 20, 2018: Schizophrenia Bulletin
Chandrashekhar D Borkar, Ashish P Bharne, B Nagalakshmi, Amul J Sakharkar, Nishikant K Subhedar, Dadasaheb M Kokare
Exaggerated thoughts, diminished mood and impaired cognition are the hallmarks of the schizophrenia-like condition. These symptoms are attributed to the dysregulation of dopamine and glutamate signaling in the brain. Since cocaine- and amphetamine-regulated transcript peptide (CART) modulates actions of dopamine as well as glutamate, we tested the role of this peptide in MK-801 induced schizophrenic dementia-like condition. MK-801 treated rats were allowed to interact with conspecific juvenile and tested for short-term (30-min) and long-term (24-hr) social memory acquisition and recall...
February 6, 2018: Neuroscience
Amrita Mishra, Arun K Mishra, Shivesh Jha
OBJECTIVE: Brahmi vati (BV) is an Ayurvedic polyherbal formulation used since ancient times and has been prescribed in seizures associated with schizophrenia and related memory loss by Ayurvedic practitioners in India. The aim of the study was to investigate these claims by evaluation of anticonvulsant, antischizophreniac, and memory-enhancing activities. Antioxidant condition of brain was determined by malondialdehyde (MDA) and reduced glutathione (GSH) levels estimations. Acetylcholinesterase (AChE) was quantitatively estimated in the brain tissue...
February 1, 2018: Epilepsy & Behavior: E&B
Joseph T Coyle, Darrick T Balu
The N-methyl-d-aspartate receptor (NMDAR) is unique in requiring two agonists to bind simultaneously to open its cation channel: the neurotransmitter, glutamate, and the coagonists, glycine, or d-serine. The Snyder laboratory was the first to clone serine racemase (SR), the enzyme that synthesizes d-serine, and to localize it immunocytochemically. Our laboratory has focused on the role of d-serine in brain disorders. Silencing the expression of SR, a risk gene for schizophrenia (SCZ), in mice (SR-/-), results in a phenotype that closely resembles SCZ including: cortical atrophy, reduced dendritic spine density and complexity, downregulation of parvalbumin-positive cortical GABAergic neurons, and cognitive impairments...
2018: Advances in Pharmacology
Clifford M Cassidy, Peter D Balsam, Jodi J Weinstein, Rachel J Rosengard, Mark Slifstein, Nathaniel D Daw, Anissa Abi-Dargham, Guillermo Horga
Hallucinations, a cardinal feature of psychotic disorders such as schizophrenia, are known to depend on excessive striatal dopamine. However, an underlying cognitive mechanism linking dopamine dysregulation and the experience of hallucinatory percepts remains elusive. Bayesian models explain perception as an optimal combination of prior expectations and new sensory evidence, where perceptual distortions such as illusions and hallucinations may occur if prior expectations are afforded excessive weight. Such excessive weight of prior expectations, in turn, could stem from a gain-control process controlled by neuromodulators such as dopamine...
February 19, 2018: Current Biology: CB
Kazuhito Nakao, Vivek Jeevakumar, Sunny Zhihong Jiang, Yuko Fujita, Noelia B Diaz, Carlos A Pretell Annan, Karen L Eskow Jaunarajs, Kenji Hashimoto, Juan E Belforte, Kazu Nakazawa
Amphetamine-induced augmentation of striatal dopamine and its blunted release in prefrontal cortex (PFC) is a hallmark of schizophrenia pathophysiology. Although N-methyl-D-aspartate receptor (NMDAR) hypofunction is also implicated in schizophrenia, it remains unclear whether NMDAR hypofunction leads to dopamine release abnormalities. We previously demonstrated schizophrenia-like phenotypes in GABAergic neuron-specific NMDAR hypofunctional mutant mice, in which Ppp1r2-Cre dependent deletion of indispensable NMDAR channel subunit Grin1 is induced in corticolimbic GABAergic neurons including parvalbumin (PV)-positive neurons, in postnatal development, but not in adulthood...
January 31, 2018: Schizophrenia Bulletin
Damiana Leo, Ilya Sukhanov, Francesca Zoratto, Placido Illiano, Lucia Caffino, Fabrizio Sanna, Giulia Messa, Marco Emanuele, Alessandro Esposito, Maria Dorofeikova, Evgeny A Budygin, Liudmila Mus, Evgenia E Efimova, Marco Niello, Stefano Espinoza, Tatyana D Sotnikova, Marius C Hoener, Gianni Laviola, Fabio Fumagalli, Walter Adriani, Raul R Gainetdinov
Dopamine (DA) controls many vital physiological functions and is critically involved in several neuropsychiatric disorders such as schizophrenia and attention deficit hyperactivity disorder (ADHD). The major function of the plasma membrane dopamine transporter (DAT) is the rapid uptake of released DA into presynaptic nerve terminals leading to control of both the extracellular levels of DA and the intracellular stores of DA. Here, we present a newly developed strain of rats (DAT-knockout, DAT-KO rats) in which the gene encoding the DAT has been disrupted by using zinc finger nuclease technology (ZFN)...
January 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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
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
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
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
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
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
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...
January 15, 2018: Journal of Neuroimmunology
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
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 the sensitivity to, procognitive 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...
March 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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
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
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