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Ketamine drug dependence

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https://www.readbyqxmd.com/read/28244984/schizophrenia-like-phenotypes-in-mice-with-nmda-receptor-ablation-in-intralaminar-thalamic-nucleus-cells-and-gene-therapy-based-reversal-in-adults
#1
K Yasuda, Y Hayashi, T Yoshida, M Kashiwagi, N Nakagawa, T Michikawa, M Tanaka, R Ando, A Huang, T Hosoya, T J McHugh, M Kuwahara, S Itohara
In understanding the mechanism of schizophrenia pathogenesis, a significant finding is that drug abuse of phencyclidine or its analog ketamine causes symptoms similar to schizophrenia. Such drug effects are triggered even by administration at post-adolescent stages. Both drugs are N-methyl-d-aspartate receptor (NMDAR) antagonists, leading to a major hypothesis that glutamate hypofunction underlies schizophrenia pathogenesis. The precise region that depends on NMDAR function, however, is unclear. Here, we developed a mouse strain in which NMDARs in the intralaminar thalamic nuclei (ILN) were selectively disrupted...
February 28, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28215996/morphological-and-behavioral-responses-of-zebrafish-after-24h-of-ketamine-embryonic-exposure
#2
Luís M Félix, Cindy Serafim, Maria J Martins, Ana M Valentim, Luís M Antunes, Manuela Matos, Ana M Coimbra
Ketamine, one anesthetic used as an illicit drug, has been detected both in freshwater and marine ecosystems. However, knowledge of its impact on aquatic life is still limited. This study aimed to test its effects in zebrafish embryos by analyzing its time- and dose-dependent developmental toxicity and long-term behavioral changes. The 24h-LC50 was calculated from percent survival using probit analysis. Based on the 24h-LC50 (94.4mgL(-1)), embryos (2hour post-fertilization - hpf) were divided into four groups, including control, and exposed for 24h to ketamine concentrations of 50, 70 or 90mgL(-1)...
February 17, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28190661/the-novel-antipsychotic-drug-brexpiprazole-alone-and-in-combination-with-escitalopram-facilitates-prefrontal-glutamatergic-transmission-via-a-dopamine-d1-receptor-dependent-mechanism
#3
Carl Björkholm, Monica M Marcus, Åsa Konradsson-Geuken, Kent Jardemark, Torgny H Svensson
Brexpiprazole (Rexulti(®)), a novel D2/3 receptor (R) partial agonist, was recently approved as monotherapy for schizophrenia, demonstrating effectiveness against both positive and negative symptoms, and also approved as add-on treatment to antidepressant drugs, inducing a potent antidepressant effect with a faster onset compared to an antidepressant given alone. Moreover, brexpiprazole has demonstrated pro-cognitive effects in preclinical studies. To explore whether the observed effects may be mediated via modulation of prefrontal glutamatergic transmission, we investigated the effect of brexpiprazole, alone and in combination with the SSRI escitalopram, on prefrontal glutamatergic transmission using in vitro electrophysiological intracellular recordings of deep layer pyramidal cells of the rat medial prefrontal cortex (mPFC)...
February 9, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28150005/gauging-circadian-variation-in-ketamine-metabolism-by-real-time-breath-analysis
#4
P Martinez-Lozano Sinues, M Kohler, S A Brown, R Zenobi, R Dallmann
The time-of-day of drug application is an important factor in maximizing efficacy and minimizing toxicity. Real-time in vivo mass spectrometric breath analysis of mice was deployed to investigate time-of-day variation in ketamine metabolism. Different production rates of ketamine metabolites, including the recently described anti-depressant hydroxynorketamine, were found in opposite circadian phases. Thus, breath analysis has potential as a rapid and 3Rs (Replacement, Reduction and Refinement) conforming screening method to estimate the time-dependence of drug metabolism...
February 14, 2017: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/28124853/ketamine-future-treatment-for-unresponsive-depression
#5
M Frere, J Tepper
Major Depressive Disorder (MDD) is a debilitating mental health condition which accounts for a significant portion of worldwide disability. Historically, the suggested pharmacotherapy to treat MDD have been monoaminergic-acting antidepressants, such as SSRIs or SNRIs. These drugs can provide relief, but often take weeks to noticeably improve depressive symptoms and are not always effective, leading to a condition known as Treatment-Resistant Depression (TRD). It is believed that 50% MDD sufferers in Ireland suffer from TRD, and thus the development of improved pharmacotherapies is necessary...
September 9, 2016: Irish Medical Journal
https://www.readbyqxmd.com/read/28043916/ketamine-accelerates-fear-extinction-via-mtorc1-signaling
#6
Matthew J Girgenti, Sriparna Ghosal, Dora LoPresto, Jane R Taylor, Ronald S Duman
Impaired fear extinction contributes to the persistence of post-traumatic stress disorder (PTSD), and can be utilized for the study of novel therapeutic agents. Glutamate plays an important role in the formation of traumatic memories, and in the pathophysiology and treatment of PTSD, highlighting several possible drug targets. Recent clinical studies demonstrate that infusion of ketamine, a glutamate NMDA receptor antagonist, rapidly and significantly reduces symptom severity in PTSD patients. In the present study, we examine the mechanisms underlying the actions of ketamine in a rodent model of fear conditioning, extinction, and renewal...
December 30, 2016: Neurobiology of Disease
https://www.readbyqxmd.com/read/27982047/a-clickable-analogue-of-ketamine-retains-nmda-receptor-activity-psychoactivity-and-accumulates-in-neurons
#7
Christine Emnett, Hairong Li, Xiaoping Jiang, Ann Benz, Joseph Boggiano, Sara Conyers, David F Wozniak, Charles F Zorumski, David E Reichert, Steven Mennerick
Ketamine is a psychotomimetic and antidepressant drug. Although antagonism of cell-surface NMDA receptors (NMDARs) may trigger ketamine's psychoactive effects, ketamine or its major metabolite norketamine could act intracellularly to produce some behavioral effects. To explore the viability of this latter hypothesis, we examined intracellular accumulation of novel visualizable analogues of ketamine/norketamine. We introduced an alkyne "click" handle into norketamine (alkyne-norketamine, A-NK) at the key nitrogen atom...
December 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27979642/severe-carisoprodol-withdrawal-after-a-14-year-addiction-and-acute-overdose
#8
Kathy T Vo, Howard Horng, Craig G Smollin, Neal L Benowitz
BACKGROUND: Carisoprodol, a centrally acting muscle relaxant with a high abuse potential, has barbiturate-like properties at the GABA-A receptor, leading to central nervous system depression and desired effects. Its tolerance and dependence has been previously demonstrated in an animal model, and withdrawal has been described in several recent case reports. Many cases can be effectively managed with a short course of benzodiazepines or antipsychotic agents. However, abrupt cessation in a patient with a history of long-term and high-dose carisoprodol abuse may result in symptoms that are more difficult for providers to treat...
December 12, 2016: Journal of Emergency Medicine
https://www.readbyqxmd.com/read/27968884/psychiatric-symptoms-in-individuals-who-use-ketamine-versus-methamphetamine-implications-for-glutamatergic-and-dopaminergic-model-for-schizophrenia-a-cohort-study
#9
Yanhui Liao, Chang Qi, Qiuxia Wu, Jinsong Tang
BACKGROUND: Both ketamine and methamphetamine have been used for studying the positive, negative, and cognitive symptoms, and dopaminergic and GABAergic dysfunction observed in acute schizophrenia. We aimed to explore and compare the prevalence and factor structure of psychotic symptoms in chronic ketamine and methamphetamine users. METHODS: We recruited chronic ketamine and methamphetamine users from the Guangzhou Baiyun and Kangda voluntary drug rehabilitation centres in the Hunan Province, China...
October 2016: Lancet
https://www.readbyqxmd.com/read/27951451/electroencephalographic-study-of-chlorpromazine-alone-or-combined-with-alpha-lipoic-acid-in-a-model-of-schizophrenia-induced-by-ketamine-in-rats
#10
Luis Rafael Leite Sampaio, Lucas Teixeira Nunes Borges, Talita Matias Barbosa, Natalia Castelo Branco Matos, Ricardo de Freitas Lima, Mariana Nascimento de Oliveira, Viviane Nóbrega Gularte, Manoel Cláudio Azevedo Patrocínio, Danielle Macêdo, Otoni Cardoso do Vale, Silvânia Maria Mendes de Vasconcelos
Schizophrenia is characterized by behavioral symptoms, brain function impairments and electroencephalographic (EEG) changes. Dysregulation of immune responses and oxidative imbalance underpins this mental disorder. The present study aimed to investigate the effects of the typical antipsychotic chlorpromazine (CP) alone or combined with the natural antioxidant alpha-lipoic acid (ALA) on changes in the hippocampal average spectral power induced by ketamine (KET). Three days after stereotactic implantation of electrodes, male Wistar rats were divided into groups treated for 10 days with saline (control) or KET (10 mg/kg, IP)...
March 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/27934938/changes-in-hippocampal-ampa-receptors-and-cognitive-impairments-in-chronic-ketamine-addiction-models-another-understanding-of-ketamine-cns-toxicity
#11
Runtao Ding, Yanning Li, Ao Du, Hao Yu, Bolin He, Ruipeng Shen, Jichuan Zhou, Lu Li, Wen Cui, Guohua Zhang, Yan Lu, Xu Wu
Ketamine has been reported to impair human cognitive function as a recreational drug of abuse. However, chronic effects of ketamine on central nervous system need to be further explored. We set out to establish chronic ketamine addiction models by giving mice a three or six month course of daily intraperitoneal injections of ketamine, then examined whether long-term ketamine administration induced cognition deficits and changed hippocampal post-synaptic protein expression in adult mice. Behavior tests results showed that mice exhibited dose- and time-dependent learning and memory deficits after long-term ketamine administration...
December 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27931319/subcutaneous-compared-with-intraperitoneal-ketaminexylazine-for-anesthesia-of-mice
#12
Maya Levin-Arama, Lital Abraham, Trevor Waner, Alon Harmelin, David M Steinberg, Tal Lahav, Mickey Harlev
Mice are commonly anesthetized intraperitoneally with a ketamine-xylazine (KX) solution. Although this route of administration allows rapid uptake of the injected drugs, its disadvantages and potential risks include pain, peritoneal irritation, and perforation of an abdominal organ; some of the risks depend on the operator's experience. We compared the efficacy of intraperitoneal and subcutaneous administration of KX in HSD:ICR, BALB/cOlaHsd, and C57BL/6JOlaHsd mice in terms of time to onset and duration of surgical anesthesia, procedure safety, and mortality...
November 2016: Journal of the American Association for Laboratory Animal Science: JAALAS
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/27890484/25-years-of-advances-in-the-definition-classification-and-treatment-of-status-epilepticus
#14
REVIEW
Eugen Trinka, Reetta Kälviäinen
PURPOSE: Status epilepticus (SE) requires not only urgent symptomatic treatment with antiepileptic drugs but also rapid identification and treatment of its cause. This narrative review summarizes the most important advances in classification and treatment of SE. METHOD: Data sources included MEDLINE, EMBASE, ClinicalTrials.gov, and back tracking of references in pertinent studies, reviews, and books. RESULTS: SE is now defined as "a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1)...
January 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/27881347/-effect-of-rhynchophylline-on-behaviors-of-methamphetamine-dependent-zebrafish-and-the-mechanism
#15
Yi-Fei Chen, Ju Peng, Miao Fang, Yi Liu, Ling-Hui Nie, Zhi-Xian Mo, Ling-Ling Zhu
OBJECTIVE: To observe the effect of rhynchophylline on methamphetamine-dependent zebrafish and explore the possible mechanism. METHODS: Zebrafish were divided into control group, amphetamine group, low- (50 mg/kg) and high (100 mg/kg)-dose rhynchophylline groups, and ketamine (150 mg/kg) group. Conditioned place preference (CPP) was induced in zebrafish with methamphetamine, and the staying time in the drug box and the tracking map of the zebrafish were observed with Noldus Ethovision XT system...
November 20, 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/27837330/reinforcing-properties-of-an-intermittent-low-dose-of-ketamine-in-rats-effects-of-sex-and-cycle
#16
Katherine N Wright, Caroline E Strong, Marjorie N Addonizio, Naomi C Brownstein, Mohamed Kabbaj
RATIONALE: Repeated intermittent exposure to ketamine has rapid and long-lasting antidepressant effects, but the abuse potential has only been assessed at high doses. Furthermore, while females are more susceptible to depression and more sensitive to ketamine's antidepressant-like effects, the abuse potential for ketamine in females is unknown. OBJECTIVES: The objectives of this study are to determine the reinforcing properties of low-dose intermittent ketamine in adult rats of both sexes and determine whether cycling gonadal hormones influence females' response to ketamine...
February 2017: Psychopharmacology
https://www.readbyqxmd.com/read/27821870/disinhibition-of-somatostatin-positive-gabaergic-interneurons-results-in-an-anxiolytic-and-antidepressant-like-brain-state
#17
T Fuchs, S J Jefferson, A Hooper, P-Hp Yee, J Maguire, B Luscher
Major depressive disorder (MDD) is associated with reduced concentrations of γ-aminobutyric acid (GABA) that are normalized by antidepressant therapies. Moreover, depressive-like phenotypes of GABAA receptor mutant mice can be reversed by treatment with conventional antidepressants drugs, as well as by subanesthetic doses of ketamine. Thus GABAergic deficits may causally contribute to depressive disorders, while antidepressant therapies may enhance GABAergic synaptic transmission. Here we tested the hypothesis that sustained enhancement of GABAergic transmission alone is sufficient to elicit antidepressant-like behavior, using disinhibition of GABAergic interneurons...
November 8, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27796754/ketamine-self-administration-reduces-the-homeostasis-of-the-glutamate-synapse-in-the-rat-brain
#18
Lucia Caffino, Alessandro Piva, Giuseppe Giannotti, Marzia Di Chio, Francesca Mottarlini, Marco Venniro, David T Yew, Cristiano Chiamulera, Fabio Fumagalli
Ketamine is a non-competitive antagonist of the NMDA glutamate receptor with psychotomimetic and reinforcing properties, although recent work has pointed out its antidepressant action following acute exposure. Our aim was to investigate the expression of crucial components of the glutamate synapse following chronic ketamine self-administration (S/A), focusing our attention on medial prefrontal cortex (mPFC) and hippocampus (Hip), two brain regions involved in compulsive drug-seeking and drug-related cognitive disorders...
October 29, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27763887/role-of-cytochrome-p4502b6-polymorphisms-in-ketamine-metabolism-and-clearance
#19
Lesley K Rao, Alicia M Flaker, Christina C Friedel, Evan D Kharasch
BACKGROUND: At therapeutic concentrations, cytochrome P4502B6 (CYP2B6) is the major P450 isoform catalyzing hepatic ketamine N-demethylation to norketamine in vitro. The CYP2B6 gene is highly polymorphic. The most common variant allele, CYP2B6*6, is associated with diminished hepatic CYP2B6 expression and catalytic activity compared with wild-type CYP2B6*1/*1. CYP2B6.6, the protein encoded by the CYP2B6*6 allele, and liver microsomes from CYP2B6*6 carriers had diminished ketamine metabolism in vitro...
December 2016: Anesthesiology
https://www.readbyqxmd.com/read/27747877/behavioral-pharmacology-of-the-odor-span-task-effects-of-flunitrazepam-ketamine-methamphetamine-and-methylphenidate
#20
Mark Galizio, Brooke April, Melissa Deal, Andrew Hawkey, Danielle Panoz-Brown, Ashley Prichard, Katherine Bruce
The Odor Span Task is an incrementing non-matching-to-sample procedure that permits the study of behavior under the control of multiple stimuli. Rats are exposed to a series of odor stimuli and selection of new stimuli is reinforced. Successful performance thus requires remembering which stimuli have previously been presented during a given session. This procedure has been frequently used in neurobiological studies as a rodent model of working memory; however, only a few studies have examined the effects of drugs on performance in this task...
November 2016: Journal of the Experimental Analysis of Behavior
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