Read by QxMD icon Read


Alexander J Riordan, Ari W Schaler, Jenny Fried, Tracie A Paine, Janice E Thornton
The cognitive symptoms of schizophrenia are poorly understood and difficult to treat. Estrogens may mitigate these symptoms via unknown mechanisms. To examine these mechanisms, we tested whether increasing estradiol (E) or decreasing luteinizing hormone (LH) could mitigate short-term episodic memory loss in a phencyclidine (PCP) model of schizophrenia. We then assessed whether changes in cortical or hippocampal GABA may underlie these effects. Female rats were ovariectomized and injected subchronically with PCP...
February 27, 2018: Psychoneuroendocrinology
Ishan Gupta, Andrew M J Young
The non-competitive glutamate antagonist, phencyclidine is used in rodents to model behavioural deficits see in schizophrenia. Importantly, these deficits endure long after the cessation of short-term chronic treatment (sub-chronic), indicating that the drug treatment causes long-term changes in the physiology and/or chemistry of the brain. There is evidence that this may occur through glutamatergic modulation of mesolimbic dopamine release, perhaps involving metabotropic glutamate receptors (mGluR). This study sought to investigate the effect of sub-chronic phencyclidine pretreatment on modulation of dopamine neurotransmission by metabotropic glutamate receptors 2 and 5 (mGluR2 and mGluR5) in the nucleus accumbens shell in vitro, with the hypothesis that phencyclidine pretreatment would disrupt the mGluR-mediated modulation of dopamine release...
March 7, 2018: Brain Research
Lih-Chu Chiou, Hsin-Jung Lee, Margot Ernst, Wei-Jan Huang, Jui-Feng Chou, Hon-Lie Chen, Akihiro Mouri, Liang-Chieh Chen, Marco Treven, Takayoshi Mamiya, Pi-Chuan Fan, Daniel E Knutson, Chris Witzigmann, James Cook, Werner Sieghart, Toshitaka Nabeshima
BACKGROUND AND PURPOSE: The pathophysiological role of α6 subunit-containing GABAA receptors (α6GABAA Rs), which are mainly expressed in cerebellar granule cells, remains unclear. Recently, we demonstrated that hispidulin, a flavonoid isolated from a local herb that remitted a patient's intractable motor tics, attenuated methamphetamine-induced hyperlocomotion in mice as a positive allosteric modulator (PAM) of cerebellar α6GABAA Rs. Here, using hispidulin and a selective α6GABAA R PAM, the pyrazoloquinolinone Compound 6, we revealed an unprecedented role of cerebellar α6GABAA Rs in disrupted prepulse inhibition (PPI), which reflects sensorimotor gating deficits manifested in several neuropsychiatric disorders...
March 8, 2018: British Journal of Pharmacology
Liang Shan, Tiane Liu, Zhijian Zhang, Qing Liu, Mengjiao Zhang, Xudong Zhao, Yan Zhang, Fuqiang Xu, Yuanye Ma
Deficits in olfactory abilities are frequently observed in schizophrenia patients. However, whether olfactory dysfunction is found in animal models is not known. Here, we examined whether two well-established schizophrenia rat models exhibit olfactory-relevant dysfunction that is similar to schizophrenia patients. Olfactory sensitivity was tested in rats that were acutely (3.3mg/kg) or postnatally (10mg/kg, at postnatal day 7, 9 and 11) treated with phencyclidine (PCP) as schizophrenia models. Electrophysiological recordings were conducted to measure the olfactory-relevant local field potential after acute PCP treatment...
March 3, 2018: Schizophrenia Research
Emilia Tarland, Jan Brosda
The olfactory system participates in many sensory processes, and olfactory endophenotypes appear in a variety of neurological disorders such as Alzheimer's and Parkinson's disease, depression and schizophrenia. Social withdrawal is a core negative symptom of schizophrenia and animal models have proven to be invaluable for studying the neurobiological mechanisms and cognitive processes behind the formation of social relationships. The subchronic phencyclidine (PCP) rat model is a validated model for negative symptoms of schizophrenia, such as impaired sociability...
February 24, 2018: Behavioural Brain Research
Markus R Meyer
This summarizing and descriptive review article is an update on previously published reviews. It covers English-written and PubMed-listed review articles and original studies published between May 2016 and November 2017 on the toxicokinetics of new psychoactive substances (NPS). Compounds covered include stimulants and entactogens, synthetic cannabinoids, tryptamines, phenethylamine and phencyclidine-like drugs, benzodiazepines, and opioids. First, an overview and discussion is provided on selected review articles followed by an overview and discussion on selected original studies...
February 24, 2018: Handbook of Experimental Pharmacology
Samuel A Barnes, Jared W Young, Athina Markou, Nika Adham, István Gyertyán, Béla Kiss
RATIONALE: Attentional processing deficits are a core feature of schizophrenia, likely contributing to the persistent functional and occupational disability observed in patients with schizophrenia. The pathophysiology of schizophrenia is hypothesized to involve dysregulation of NMDA receptor-mediated glutamate transmission, contributing to disruptions in normal dopamine transmission. Preclinical investigations often use NMDA receptor antagonists, such as phencyclidine (PCP), to induce cognitive disruptions relevant to schizophrenia...
February 22, 2018: Psychopharmacology
Masato Nakashima, Haruka Imada, Eri Shiraishi, Yuki Ito, Noriko Suzuki, Maki Miyamoto, Takahiko Taniguchi, Hiroki Iwashita
The pathophysiology of schizophrenia has been associated with glutamatergic dysfunction. Modulation of the glutamatergic signaling pathway, including N-methyl-D-aspartate (NMDA) receptors, can provide a new therapeutic target for schizophrenia. Phosphodiesterase 2A (PDE2A) is highly expressed in the forebrain, and is a dual substrate enzyme that hydrolyzes both cAMP and cGMP, which play pivotal roles as intracellular second messengers downstream of NMDA receptors. Here we characterize the in vivo pharmacological profile of a selective and brain penetrant PDE2A inhibitor, (N-{(1S)-1-[3-fluoro-4-(trifluoromethoxy)phenyl]-2-methoxyethyl}-7-methoxy-2-oxo-2,3-dihydropyrido[2,3-b]pyrazine-4(1H)-carboxamide) (TAK-915) as a novel treatment for schizophrenia...
February 13, 2018: Journal of Pharmacology and Experimental Therapeutics
Jacob J van den Berg, Samuel Adeyemo, Mary B Roberts, Beth C Bock, L A R Stein, Rosemarie A Martin, Donna R Parker, Jennifer G Clarke
BACKGROUND: Problems with self-reported drug use include difficulties with recall and recognition as well as the desire to respond to questions in a socially desirable manner. Various methods have been developed to improve and/or validate estimates based on direct questioning of individuals regarding their substance use. For this study, we were interested in validating self-reported use of: 1) tobacco, 2) marijuana, and 3) other substances (i.e., heroin, cocaine, opiates, oxycodone, benzodiazepines, methamphetamine, phencyclidine, and barbiturates) employing urinalysis among inmates who participated in a randomized controlled trial of a smoking abstinence intervention in a tobacco-free prison located in the northeastern United States...
February 8, 2018: Substance Use & Misuse
Matteo Caloro, Giuseppa Calabrò, Eleonora de Pisa, Enrico Rosini, Georgios D Kotzalidis, Davide Lonati, Carlo Alessandro Locatelli, Pietro Papa, Fabrizio Schifano, Paolo Girardi
: Novel psychoactive substance use is a major social concern. Their use may elicit or uncover unpredictably as yet undescribed clinical pictures. We aimed to illustrate a multisubstance use case indistinguishable from paranoid schizophrenia, so to alert clinicians on possibly misdiagnosing substance-induced psychotic disorders. CASE REPORT: We describe a case of a 32-year-old man who started at 18 years with cannabinoids and ketamine, and is currently using N-methyl-D-aspartate (NMDA) antagonists...
February 2, 2018: Journal of Addiction Medicine
Michael J Mathews, Ralph N Mead, Mark Galizio
The glutamate hypothesis proposes that N-Methyl-D-aspartate (NMDA) receptor hypofunction underlies cognitive and perhaps other schizophrenic symptoms. The present study used the odor span task to assess the effects of NMDA antagonists on remembering multiple stimuli in rodents. This task uses an incrementing nonmatching-to-sample procedure in which responses to a new olfactory stimulus are reinforced on each trial, whereas responses to previously presented stimuli are not. NMDA antagonists have been associated with memory impairments in a variety of animal models; however, there are inconsistencies across different NMDA antagonists and tasks used...
February 2018: Experimental and Clinical Psychopharmacology
Dan Ma, Paul C Guest
Under- or overfeeding during pregnancy can lead to behavioral deficits in the offspring in later life. Here, we present a protocol for setting up and carrying out the hyperlocomotion test for assessing behavioral symptoms such as psychosis or mania. As an example, we use the acute rat phencyclidine-injection model which exhibits hyperlocomotion and stereotypic behaviors, resembling the positive symptoms of schizophrenia.
2018: Methods in Molecular Biology
Bernhard Wünsch, Louisa Temme, Dirk Schepmann, Julian A Schreiber, Bastian Frehland
Since only a few studies investigated the affinity and functional activity of NMDA receptor open channel blockers under same assay conditions, a comparative study of common open channel blockers is of major interest. The pharmacological activity of MK-801, phencyclidine, dexoxadrol, etoxadrol, (S)- and (R)-ketamine, dextromethorphan, memantine and amantadine was analyzed under same uniform assay conditions. The affinity towards the PCP and ifenprodil binding sites was recorded in radioligand binding assays...
January 27, 2018: ChemMedChem
Mingshuo Xu, Yu Wang, Feipu Yang, Chunhui Wu, Zhen Wang, Bin Ye, Xiangrui Jiang, Qingjie Zhao, Jianfeng Li, Yongjian Liu, Junchi Zhang, Guanghui Tian, Yang He, Jingshan Shen, Hualiang Jiang
In the present study, a series of multi-target N-substituted cyclic imide derivatives which possessed potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties were synthesized and evaluated as potential antipsychotics. Among these compounds, (3aR,4R,7S,7aS)-2-(4-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)butyl)-3a,4,7,7a-tetrahydro-1H-4,7-methanoisoindole-1,3(2H)-dione hydrochloride (3d) held a promising pharmacological profile. 3d not only showed potent and balanced in vitro activities on D2/5-HT1A/5-HT2A receptors, but also endowed with low to moderate activities on 5-HT2C, H1, α1A, M3 receptors and hERG channel, suggesting a low liability to induce side effects such as weight gain, orthostatic hypotension and QT prolongation...
January 4, 2018: European Journal of Medicinal Chemistry
Bridgette Martinak, Ramy A Bolis, Jeffrey Ryne Black, Rachel E Fargason, Badari Birur
Dextromethorphan (3-methoxy-N-methylmorphinan), also known as "DXM" and "the poor man's PCP," is a synthetically produced drug that is available in more than 140 over-the-counter cough and cold preparations. Dextromethorphan (DXM) has overtaken codeine as the most widely used cough suppressant due to its availability, efficacy, and safety profile at directed doses. However, DXM is subject to abuse. When consumed at inappropriately high doses (over 1500 mg/day), DXM can induce a state of psychosis characterized by Phencyclidine (PCP)-like psychological symptoms, including delusions, hallucinations, and paranoia...
September 15, 2017: Psychopharmacology Bulletin
David Vanda, Miroslav Soural, Vittorio Canale, Séverine Chaumont-Dubel, Grzegorz Satała, Tomasz Kos, Petr Funk, Veronika Fülöpová, Barbora Lemrová, Paulina Koczurkiewicz, Elżbieta Pękala, Andrzej J Bojarski, Piotr Popik, Philippe Marin, Paweł Zajdel
A small library of novel 3H-imidazo[4,5-b]pyridine and 1H-imidazo[4,5-c]pyridine derivatives was designed and synthesized as non-sulfonamide 5-HT6 receptor ligands. In vitro evaluation allowed to identify compound 17 (2-ethyl-3-(3-fluorobenzyl)-7-(piperazin-1-yl)-3H-imidazo[4,5-b]pyridine) as potent 5-HT6 receptor partial inverse agonist in Gs signaling (Ki = 6 nM, IC50 = 17.6 nM). Compound 17 displayed high metabolic stability, favorable cytochrome P450 isoenzyme (2D6, 3A4) profile, did not affect PgP-protein binding, without evoking mutagenic effects...
December 16, 2017: European Journal of Medicinal Chemistry
Nichole M Neugebauer, Masanori Miyauchi, Tatsuya Sato, Jun Tadano, Hanife Akal, Hossein Ardehali, Herbert Y Meltzer
BACKGROUND: Abnormalities in prefrontal cortical and hippocampal GABAergic function are postulated to be major causes of the cognitive impairment associated with schizophrenia (CIAS). There are conflicting views on whether diminished or enhanced GABAergic activity contributes to the deficit in short-term novel object recognition (NOR) in the sub-chronic phencyclidine (scPCP) rodent model of CIAS. This study assessed the role of GABAA signaling in the medial prefrontal cortex (mPFC) and ventral hippocampus (vHPC) in NOR in saline (scSAL)- and scPCP-treated rats...
December 28, 2017: Behavioural Brain Research
Junhui Liu, Wei Zhang, Jinteng Feng, Min Jia, Guangjian Zhang, Xiaopeng Wen
5-hydroxytryptamine7 (5-HT7) receptors in the medial prefrontal cortex (mPFC) play a critical role in complex cognitive impairment in schizophrenia. The mouse model of schizophrenia was established through the neonatal administration of phencyclidine (nPCP). Recombinant adeno-associated virus-mediated gene knockdown was used to investigate the role of mPFC 5-HT7 receptor in the schizophrenia-like symptoms in mice. Under baseline conditions in the 5-choice serial reaction time task (5-CSRTT), nPCP produced a significant attentional impairment that was exacerbated when mice were tested under LITI...
December 23, 2017: Behavioural Brain Research
Triniti L Scroggin, Gwendolyn A McMillin
In this study, a quantitative polarity switching liquid chromatography coupled with a tandem mass spectrometer (LC-MS/MS) method was developed to detect and quantify cocaine and metabolites (cocaethylene, benzoylecgonine and meta-hydroxybenzoylecgonine), phencyclidine (PCP) and barbiturates (phenobarbital and butalbital) in meconium. Accuracy and precision samples at 0.0125% and 75% of the upper limit of quantitation (ULOQ) were analyzed in triplicate over 5 days with accuracy above 84% and average %CV values below 11%...
December 13, 2017: Journal of Analytical Toxicology
Bonnie L Robinson, Melanie Dumas, Syed F Ali, Merle G Paule, Qiang Gu, Jyotshna Kanungo
Ketamine, a phencyclidine derivative, is an antagonist of the Ca2+ -permeable N-methyl-d-aspartate (NMDA)-type glutamate receptors. It is a pediatric anesthetic and has been implicated in developmental neurotoxicity. Ketamine has also been shown to deplete ATP in mammalian cells. Our previous studies showed that acetyl l-carnitine (ALCAR) prevented ketamine-induced cardiotoxicity and neurotoxicity in zebrafish embryos. Based on our finding that ALCAR's protective effect was blunted by oligomycin A, an inhibitor of ATP synthase, we further investigated the effects of ketamine and ALCAR on ATP levels, mitochondria and ATP synthase in zebrafish embryos...
December 7, 2017: Neurotoxicology and Teratology
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"