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Schizophrenia psychostimulants

Danielle E Rastedt, Roxanne A Vaughan, James D Foster
The neurotransmitter dopamine (DA) plays a key role in several biological processes including reward, mood, motor activity and attention. Synaptic DA homeostasis is controlled by the dopamine transporter (DAT) which transports extracellular DA into the presynaptic neuron after release and regulates its availability to receptors. Many neurological disorders such as schizophrenia, bipolar disorder, Parkinson disease and attention-deficit hyperactivity disorder are associated with imbalances in DA homeostasis that may be related to DAT dysfunction...
January 20, 2017: Journal of Chemical Neuroanatomy
Neal R Swerdlow, Melissa Tarasenko, Savita G Bhakta, Jo Talledo, Alexis I Alvarez, Erica L Hughes, Brinda Rana, Sophia Vinogradov, Gregory A Light
Targeted cognitive training (TCT) of auditory processing enhances higher-order cognition in schizophrenia patients. TCT performance gains can be detected after 1 training session. As a prelude to a potential clinical trial, we assessed a pharmacological augmentation of cognitive therapy (PACT) strategy by testing if the psychostimulant, amphetamine, augments TCT gains in auditory processing speed (APS) in schizophrenia patients and healthy subjects (HS). HS and schizophrenia patients were tested in a screening session (test 1), followed by a double-blind crossover design (tests 2-3), comparing placebo vs amphetamine (10 mg; 7 d between tests)...
October 25, 2016: Schizophrenia Bulletin
Nao Chuhma, Susana Mingote, Abigail Kalmbach, Leora Yetnikoff, Stephen Rayport
Brain imaging has revealed alterations in dopamine uptake, release, and receptor levels in patients with schizophrenia that have been resolved on the scale of striatal subregions. However, the underlying synaptic mechanisms are on a finer scale. Dopamine neuron synaptic actions vary across the striatum, involving variations not only in dopamine release but also in dopamine neuron connectivity, cotransmission, modulation, and activity. Optogenetic studies have revealed that dopamine neurons release dopamine in a synaptic signal mode, and that the neurons also release glutamate and gamma-aminobutyric acid as cotransmitters, with striking regional variation...
January 1, 2017: Biological Psychiatry
Travis A Wearne, Lindsay M Parker, Jane L Franklin, Ann K Goodchild, Jennifer L Cornish
Psychotic disorders, such as schizophrenia, are characterized by prevalent and persistent executive deficits that are believed to be the result of dysfunctional inhibitory gamma-aminobutyric acid (GABA) processing of the prefrontal cortex (PFC). Methamphetamine (METH) is a commonly used psychostimulant that can induce psychotic and cognitive symptoms that are indistinguishable to schizophrenia, suggesting that METH-induced psychosis may have a similar GABAergic profile of the PFC. As the PFC consists of multiple subregions, the aim of the current study was to investigate changes to GABAergic mRNA expression in the prelimbic (PRL) and orbitofrontal (OFC) cortices of the PFC in rats sensitized to repeated METH administration...
December 2016: Neuropharmacology
Masahide Fukada, Atsuo Nakayama, Takayoshi Mamiya, Tso-Pang Yao, Yoshiharu Kawaguchi
Histone deacetylase 6 (Hdac6), a multifunctional cytoplasmic deacetylase, is abundant in brain. We previously demonstrated that global Hdac6 depletion causes aberrant emotional behaviors in mice. Identification of affected brain systems and its molecular basis will lead to new insights into relations between protein acetylation events and psychiatric disorders. Here we report the dopaminergic abnormalities in Hdac6 KO mice. The dopamine transmission mediated by D1-like and D2-like G protein-coupled dopamine receptors is known to play roles in controlling movement, cognition, and motivational processes, and its dysfunction causes psychiatric disorders...
November 2016: Neuropharmacology
Taylor S Willi, Donna J Lang, William G Honer, Geoff N Smith, Allen E Thornton, William J Panenka, Ric M Procyshyn, Fidel Vila-Rodriguez, Wayne Su, A Talia Vertinsky, Olga Leonova, Alexander Rauscher, G William MacEwan, Alasdair M Barr
After prolonged psychostimulant abuse, transient psychotic symptoms referred to as "substance-induced psychosis" (SIP) can develop - closely resembling symptoms observed in schizophrenia spectrum disorders. The comparability in psychotic presentation between SIP and schizophrenias suggests that similar underlying neural deficits may contribute to the expression of psychosis across these disorders. To date, neuroanatomical characterization of grey matter structural alterations in SIP has been limited to methamphetamine associated psychosis, with no studies controlling for potential neurotoxic effects of the psychostimulant that precipitates psychosis...
October 2016: Schizophrenia Research
Karly M Turner, Thomas H J Burne
RATIONALE: Attentional deficits occur in a range of neuropsychiatric disorders, such as schizophrenia and attention deficit hyperactivity disorder. Psychostimulants are one of the main treatments for attentional deficits, yet there are limited reports of procognitive effects of amphetamine in preclinical studies. Therefore, task development may be needed to improve predictive validity when measuring attention in rodents. OBJECTIVES: This study aimed to use a modified signal detection task (SDT) to determine if and at what doses amphetamine could improve attention in rats...
September 2016: Psychopharmacology
Aitor Esnal, Ana Sánchez-González, Cristóbal Río-Álamos, Ignasi Oliveras, Toni Cañete, Gloria Blázquez, Adolf Tobeña, Alberto Fernández-Teruel
The aim of the present study was to obtain further evidence supporting the validity of a new genetically-based rat model for the study of schizophrenia-relevant symptoms. The Roman high- (RHA-I) and low-avoidance (RLA-I) inbred rats have been psychogenetically selected for their rapid versus extremely poor acquisition of the two-way avoidance task in the shuttle box and present two well-differentiated profiles regarding several traits related to anxiety, impulsivity and sensitivity to (dopaminergic) psychostimulants...
September 1, 2016: Physiology & Behavior
Siriluk Veerasakul, Samur Thanoi, Gavin P Reynolds, Sutisa Nudmamud-Thanoi
Methamphetamine (METH) is a psychostimulant drug with potent effects on the central nervous system that can cause psychotic symptoms similar to those of schizophrenia. Specific alterations in GABAergic neuronal markers have been reported in schizophrenia and animal models of psychotic illness. The aim of this study was to determine whether there are changes in subpopulations of GABAergic neurons, defined by the presence of calcium binding proteins (CBPs), in animal models of METH abuse. Rats received acute (Binge) doses of 4 × 6 mg/kg, a chronic escalating dose regime (0...
October 2016: Neurotoxicity Research
Lisa L Giles, D Richard Martini
Most prescriptions for psychotropic medications are written by primary care physicians, yet pediatricians, many of whom are teaching residents and medical students about pediatric psychopharmacology, often feel inadequately trained to treat mental health concerns. Over the past several decades, the number, size, and quality of psychopharmacologic studies in youth has greatly increased. Here we review the current evidence for efficacy and safety of each of the major pharmacologic drug classes in youth (psychostimulants, antidepressants, mood stabilizers, and antipsychotics)...
August 2016: Academic Pediatrics
Jane L Franklin, Mehdi Mirzaei, Travis A Wearne, Judi Homewood, Ann K Goodchild, Paul A Haynes, Jennifer L Cornish
Caffeine is a plant-derived psychostimulant and a common additive found in a wide range of foods and pharmaceuticals. The orbitofrontal cortex (OFC) is rapidly activated by flavours, integrates gustatory and olfactory information, and plays a critical role in decision-making, with dysfunction contributing to psychopathologies and neurodegenerative conditions. This study investigated whether long-term consumption of caffeine causes changes to behavior and protein expression in the OFC. Male adult Sprague-Dawley rats (n = 8 per group) were treated for 26 days with either water or a 0...
May 6, 2016: Journal of Proteome Research
Abbes Belkhiri, Shoumin Zhu, Wael El-Rifai
Dopamine and cAMP-regulated phosphoprotein Mr 32,000 (DARPP-32), also known as phosphoprotein phosphatase-1 regulatory subunit 1B (PPP1R1B), was initially discovered as a substrate of dopamine-activated protein kinase A (PKA) in the neostriatum in the brain. While phosphorylation at Thr-34 by PKA converts DARPP-32 into a potent inhibitor of protein phosphatase 1 (PP1), phosphorylation at Thr-75 transforms DARPP-32 into an inhibitor of PKA. Through regulation of DARPP-32 phosphorylation and modulation of protein phosphatase and kinase activities, DARPP-32 plays a critical role in mediating the biochemical, electrophysiological, and behavioral effects controlled by dopamine and other neurotransmitters in response to drugs of abuse and psychostimulants...
April 5, 2016: Oncotarget
M-A Lodovighi, A Palomba, R Belzeaux, M Adida, J-M Azorin
The management of negative symptoms appears to be a major challenge because of functional disability induced by these symptoms and their relative resistance to treatments currently on the market. The aim of this article is to review new approaches that may enable optimal management of these symptoms. First, we describe the methodological difficulties that hindered the development and evaluation of specific treatment, and objectives currently defined to enable the development of new pharmacological approaches...
December 2015: L'Encéphale
Simon Zhornitsky, Andràs Tikàsz, Élie Rizkallah, Jean-Pierre Chiasson, Stéphane Potvin
Background. Substance-induced psychotic disorder (SIPD) is a diagnosis constructed to distinguish substance-induced psychotic states from primary psychotic disorders. A number of studies have compared SIPD persons with primary psychotic patients, but there is little data on what differentiates substance use disorder (SUD) individuals with and without SIPD. Here, we compared psychopathology, sociodemographic variables, and substance use characteristics between SUD patients with and without SIPD. Methods. A retrospective chart review was conducted on newly admitted patients at a rehabilitation centre between 2007 and 2012...
2015: Journal of Addiction
M A Labouesse, W Langhans, U Meyer
Impairments in central reward processing constitute an important aspect of the negative symptoms of schizophrenia. Despite its clinical relevance, the etiology of deficient reward processing in schizophrenia remains largely unknown. Here, we used an epidemiologically informed mouse model of schizophrenia to explore the effects of prenatal immune activation on reward-related functions. The model is based on maternal administration of the viral mimic PolyI:C and has been developed in relation to the epidemiological evidence demonstrating enhanced risk of schizophrenia and related disorders following prenatal maternal infection...
2015: Translational Psychiatry
Maren Carbon, Sandeep Kapoor, Eva Sheridan, Aseel Al-Jadiri, Sally Azzo, Tania Sarkaria, John M Kane, Ema Saito, Christoph U Correll
OBJECTIVE: Second-generation antipsychotic (SGA) effects in youth were monitored to quantify extrapyramidal side effects (EPS) and to identify risk profiles for treatment-emergent EPS. METHOD: Data were analyzed for the nonrandomized, prospective Second-generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth (SATIETY) inception cohort study. EPS were assessed at baseline and 4, 8, and 12 weeks after naturalistic SGA initiation for schizophrenia, mood, disruptive behavior, and autism spectrum disorders using the Simpson-Angus Scale (SAS), Barnes Akathisia Scale, Abnormal Involuntary Movement Scale (AIMS), and Treatment Emergent Side Effect Scale...
September 2015: Journal of the American Academy of Child and Adolescent Psychiatry
Elisabeth Piccart, Nicholas A Courtney, Sarah Y Branch, Christopher P Ford, Michael J Beckstead
UNLABELLED: Increased dopaminergic signaling is a hallmark of severe mesencephalic pathologies such as schizophrenia and psychostimulant abuse. Activity of midbrain dopaminergic neurons is under strict control of inhibitory D2 autoreceptors. Application of the modulatory peptide neurotensin (NT) to midbrain dopaminergic neurons transiently increases activity by decreasing D2 dopamine autoreceptor function, yet little is known about the mechanisms that underlie long-lasting effects. Here, we performed patch-clamp electrophysiology and fast-scan cyclic voltammetry in mouse brain slices to determine the effects of NT on dopamine autoreceptor-mediated neurotransmission...
August 5, 2015: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Miho Ota, Shintaro Ogawa, Koichi Kato, Chiaki Masuda, Hiroshi Kunugi
Previous studies have demonstrated that patients with schizophrenia show greater sensitivity to psychostimulants than healthy subjects. Sensitization to psychostimulants and resultant alteration of dopaminergic neurotransmission in rodents has been suggested as a useful model of schizophrenia. This study sought to examine the use of methylphenidate as a psychostimulant to induce dopamine release and that of [(18)F]fallypride as a radioligand to quantify the release in a primate model of schizophrenia. Four common marmosets were scanned by positron emission tomography twice, before and after methylphenidate challenge, to evaluate dopamine release...
December 2015: Neuroscience Research
Evangelia M Tsapakis, Trisevgeni Dimopoulou, Frank I Tarazi
Overwhelming research evidence suggests that the negative symptoms of schizophrenia (NSS) contribute more to impaired quality of life and poor functioning than positive symptoms, and that NSS, including affective flattening, alogia and avolition are present in at least one-fifth of patients diagnosed with schizophrenia. Despite this, management of NSS continues to be a major clinical unmet need as treatment with current antipsychotic medication seems to reach at best modest efficacy. A critical review of the current pharmacological, non-pharmacological and psychosocial treatments available for NSS is presented here, using data retrieved from the MEDLINE/PUBMED, the Cochrane Database of Systematic Reviews and the ClinicalTrials...
September 2015: Pharmacology & Therapeutics
Pothitos M Pitychoutis, Arnauld Belmer, Imane Moutkine, Joëlle Adrien, Luc Maroteaux
Impulsivity and hyperactivity share common ground with numerous mental disorders, including schizophrenia. Recently, a population-specific serotonin 2B (5-HT2B) receptor stop codon (ie, HTR2B Q20*) was reported to segregate with severely impulsive individuals, whereas 5-HT2B mutant (Htr2B(-/-)) mice also showed high impulsivity. Interestingly, in the same cohort, early-onset schizophrenia was more prevalent in HTR2B Q*20 carriers. However, the putative role of 5-HT2B receptor in the neurobiology of schizophrenia has never been investigated...
November 2015: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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