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Ketamine drug dependence

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https://www.readbyqxmd.com/read/28623920/ketamine-induced-apoptosis-in-the-mouse-cerebral-cortex-follows-similar-characteristic-of-physiological-apoptosis-and-can-be-regulated-by-neuronal-activity
#1
Qi Wang, Feng-Yan Shen, Rong Zou, Jing-Jing Zheng, Xiang Yu, Ying-Wei Wang
The effects of general anesthetics on inducing neuronal apoptosis during early brain development are well-documented. However, since physiological apoptosis also occurs during this developmental window, it is important to determine whether anesthesia-induced apoptosis targets the same cell population as physiological apoptosis or different cell types altogether. To provide an adequate plane of surgery, ketamine was co-administered with dexmedetomidine. The apoptotic neurons in the mouse primary somatosensory cortex (S1) were quantitated by immunohistochemistry...
June 17, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28589265/effects-of-ketamine-on-the-unconditioned-and-conditioned-locomotor-activity-of-preadolescent-and-adolescent-rats-impact-of-age-sex-and-drug-dose
#2
Sanders A McDougall, Andrea E Moran, Timothy J Baum, Matthew G Apodaca, Vanessa Real
RATIONALE: Ketamine is used by preadolescent and adolescent humans for licit and illicit purposes. OBJECTIVE: The goal of the present study was to determine the effects of acute and repeated ketamine treatment on the unconditioned behaviors and conditioned locomotor activity of preadolescent and adolescent rats. METHODS: To assess unconditioned behaviors, female and male rats were injected with ketamine (5-40 mg/kg), and distance traveled was measured on postnatal day (PD) 21-25 or PD 41-45...
June 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28481700/pediatric-status-epilepticus-improved-management-with-new-drug-therapies
#3
Alberto Verrotti, Michela Ambrosi, Piero Pavone, Pasquale Striano
Status Epilepticus (SE) is the most common neurological emergency of childhood. It requires prompt administration of appropriately selected anti-seizure medications. Areas covered: Following a distinction between estabilished and emergent drugs, we present pharmacological treatment options and their clinical utility in children, with a short mention on alternatives to drug treatment. We also propose an algorithm for the management of pediatric SE. For this review a Pubmed, Medline and Embase search was performed...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28461248/simultaneous-triple-therapy-for-the-treatment-of-status-epilepticus
#4
Jerome Niquet, Roger Baldwin, Keith Norman, Lucie Suchomelova, Lucille Lumley, Claude G Wasterlain
Early maladaptive internalization of synaptic GABAA receptors (GABAAR) and externalization of NMDA receptors (NMDAR) may explain the time-dependent loss of potency of standard anti-epileptic drugs (AED) in refractory status epilepticus (SE). We hypothesized that correcting the effects of changes in GABAAR and NMDAR would terminate SE, even when treatment is delayed 40 minutes. SE was induced in adult Sprague-Dawley rats with a high dose of lithium and pilocarpine. The GABAAR agonist midazolam, the NMDAR antagonist ketamine and the AED valproate were injected 40 min after SE onset in combination or as monotherapy...
April 29, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28458430/anesthetic-efficacy-of-ketamine-diazepam-ketamine-xylazine-and-ketamine-acepromazine-in-caspian-pond-turtles-mauremys-caspica
#5
Milad Adel, Amin Bigham Sadegh, Vincenzo Arizza, Hossein Abbasi, Luigi Inguglia, Hasan Nasrollahzadeh Saravi
OBJECTIVES: The objective of this study was to assess the efficacy of different anesthetic drug combinations on the Caspian Pond turtles (Mauremys caspica). SUBJECTS AND METHODS: Three groups of the Caspian Pond turtles (n = 6) were anesthetized with three different drug combinations. Initially, a pilot study was conducted to determine the best drug doses for the anesthetization of the turtles, and according to these results, ketamine-diazepam (120 mg/kg ketamine hydrochloride [5%] and 2 mg/kg diazepam [5%]), ketamine-acepromazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg acepromazine [1%]), and ketamine-xylazine (120 mg/kg ketamine hydrochloride [5%] and 1 mg/kg xylazine [2%]) were injected intramuscularly...
January 2017: Indian Journal of Pharmacology
https://www.readbyqxmd.com/read/28454718/effects-of-co-administration-of-ketamine-and-ethanol-on-the-dopamine-system-via-the-cortex-striatum-circuitry
#6
Qing Liu, Tian-Yong Xu, Zhi-Bi Zhang, Chi-Kwan Leung, Ding-Yun You, Shang-Wen Wang, Shuai Yi, Qiang Jing, Run-Fang Xie, Huifang-Jie Li, Xiao-Feng Zeng
AIM: Ketamine and ethanol are increasingly being used together as recreational drugs in rave parties. Their effects on the dopamine (DA) system remain largely unknown. This study aimed to investigate the effects of consuming two different concentrations of ketamine with and without alcohol on the DA system. MATERIALS AND METHODS: We employed the conditioned place preference (CPP) paradigm to evaluate the rewarding effects of the combined administration of two different doses of ketamine (30mg/kg and 60mg/kg) with ethanol (0...
April 25, 2017: Life Sciences
https://www.readbyqxmd.com/read/28396142/atypical-binding-at-dopamine-and-serotonin-transporters-contribute-to-the-discriminative-stimulus-effects-of-mephedrone
#7
Alyssa F DeLarge, Laura L Erwin, Peter J Winsauer
Mephedrone (4-methylmethcathinone), a constituent of the recreational substances known as "bath salts", is a synthetic cathinone that can produce auditory and visual hallucinations, as well as problematic cardiovascular effects. This study compared the discriminative stimulus effects of mephedrone (0.32-10 mg/kg) with other prototypical drugs of abuse: cocaine (0.56-32 mg/kg), d-amphetamine (0.18-3.2 mg/kg), ketamine (1.8-18 mg/kg), phencyclidine (PCP, 1-5.6 mg/kg), heroin (1-10 mg/kg), 2,5-dimethoxy-4-iodoamphetamine (R-DOI, 0...
June 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28389811/general-anesthetic-actions-on-gabaa-receptors-in-vivo-are-reduced-in-phospholipase-c-related-catalytically-inactive-protein-knockout-mice
#8
Masaki Hayashiuchi, Tomoya Kitayama, Katsuya Morita, Yosuke Yamawaki, Kana Oue, Taiga Yoshinaka, Satoshi Asano, Kae Harada, Youngnam Kang, Masato Hirata, Masahiro Irifune, Mitsugi Okada, Takashi Kanematsu
PURPOSE: The aim of this study was to investigate the action of general anesthetics in phospholipase C-related catalytically inactive protein (PRIP)-knockout (KO) mice that alter GABAA receptor signaling. METHODS: PRIP regulates the intracellular trafficking of β subunit-containing GABAA receptors in vitro. In this study, we examined the effects of intravenous anesthetics, propofol and etomidate that act via β subunit-containing GABAA receptors, in wild-type and Prip-KO mice...
April 7, 2017: Journal of Anesthesia
https://www.readbyqxmd.com/read/28373844/effects-of-ketamine-on-levels-of-inflammatory-cytokines-il-6-il-1%C3%AE-and-tnf-%C3%AE-in-the-hippocampus-of-mice-following-acute-or-chronic-administration
#9
Yanning Li, Ruipeng Shen, Gehua Wen, Runtao Ding, Ao Du, Jichuan Zhou, Zhibin Dong, Xinghua Ren, Hui Yao, Rui Zhao, Guohua Zhang, Yan Lu, Xu Wu
Ketamine is an injectable anesthetic and recreational drug of abuse commonly used worldwide. Many experimental studies have shown that ketamine can impair cognitive function and induce psychotic states. Neuroinflammation has been suggested to play an important role in neurodegeneration. Meanwhile, ketamine has been shown to modulate the levels of inflammatory cytokines. We hypothesized that the effects of ketamine on the central nervous system are associated with inflammatory cytokines. Therefore, we set out to establish acute and chronic ketamine administration models in C57BL/6 mice, to evaluate spatial recognition memory and emotional response, to analyze the changes in the levels of the inflammatory cytokines interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) in the mouse hippocampus, employing behavioral tests, Western blot, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28339766/higher-bioavailability-of-doxycycline-in-broiler-chickens-with-a-novel-in-feed-pharmaceutical-formulation
#10
Lilia Gutiérrez, Juan Zermeño, Yazmín Alcalá, Héctor Sumano
Bioavailability of a new, long-acting (LA) pharmaceutical preparation for administering doxycycline as in-feed medication to broiler chickens was compared to the standard in-feed administration of doxycycline. A commercial poultry house harboring Ross-308 broiler chickens, weighing 450 g, was divided into 7 sections as follows: doxy-FOLA group (n = 6,000 chickens divided into 3 replicates) medicated with 10% doxycyline, long-acting pellets at a dose of 400 g of doxycycline HCl/ton of food, resulting in a calculated dose of 48 mg/kg for 5 d; doxy-ref group (n = 6,000, divided into 3 replicates) medicated as for doxy-FOLA, but using a 20% commercial preparation of doxycycline...
February 23, 2017: Poultry Science
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
#11
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
#12
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)...
April 15, 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
#13
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)...
April 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
#14
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
#15
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
#16
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
#17
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
#18
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...
May 2017: 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
#19
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
#20
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
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