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Ketamine drug dependence

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...
October 20, 2016: Anesthesiology
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...
October 17, 2016: Journal of the Experimental Analysis of Behavior
G Daş, A Vernunft, S Görs, E Kanitz, J M Weitzel, K-P Brüssow, C C Metges
Physiological research with swine often includes sedation or general anesthesia (GA), which may influence the basal physiological responses of experimental animals and may have the potential to confound or interfere with the effects of experimental factors of interest. Using 6 adult female pigs, we investigated whether selected plasma metabolites and hormones are influenced by GA induced with ketamine (K) and 2 neuroleptic sedatives, namely azaperone (A) and xylazine (X). Fasted pigs rotationally received either no drug, a single intravenous administration of A or X, or A or X combined with ketamine (AK or XK, respectively), and plasma concentrations of glucose, lactate, non-esterified fatty acids (NEFA), triglycerides (TG), glucagon, insulin, and cortisol were determined for a 5-h period following administration...
August 2016: Journal of Animal Science
Christopher J Fitzpatrick, Jonathan D Morrow
The attribution of incentive-motivational value to reward-related cues contributes to cue-induced craving and relapse in addicted patients. Recently, it was demonstrated that subanesthetic ketamine increases motivation to quit and decreases cue-induced craving in cocaine-dependent individuals. Although the underlying mechanism of this effect is currently unknown, one possibility is that subanesthetic ketamine decreases the incentive-motivational value of reward-related cues. In the present study, we used a Pavlovian conditioned approach procedure to identify sign-trackers, rats that attribute incentive-motivational value to reward-related cues, and goal-trackers, rats that assign only predictive value to reward-related cues...
September 20, 2016: Journal of Psychopharmacology
Justin R Yates, Kerry A Breitenstein, Benjamin T Gunkel, Mallory N Hughes, Anthony B Johnson, Katherine K Rogers, Sara M Shape
Risky decision making can be measured using a probability-discounting procedure, in which animals choose between a small, certain reinforcer and a large, uncertain reinforcer. Recent evidence has identified glutamate as a mediator of risky decision making, as blocking the N-methyl-d-aspartate (NMDA) receptor with MK-801 increases preference for a large, uncertain reinforcer. Because the order in which probabilities associated with the large reinforcer can modulate the effects of drugs on choice, the current study determined if NMDA receptor ligands alter probability discounting using ascending and descending schedules...
September 15, 2016: Pharmacology, Biochemistry, and Behavior
Ashley E Lepack, Eunyoung Bang, Boyoung Lee, Jason M Dwyer, Ronald S Duman
Recent preclinical and clinical studies demonstrate that three functionally different compounds, the NMDA receptor channel blocker ketamine, mGlu2/3 receptor antagonist LY341495, and NMDA receptor glycine site agent GLYX-13 produce rapid and long lasting antidepressant effects. Furthermore, these agents are reported to stimulate ERK and mTORC1 signaling in brain. Here we used rat primary cortical culture neurons to further examine the cellular actions of these agents. The results demonstrate that low concentrations of all three compounds rapidly increase levels of the phosphorylated and activated forms of ERK and a downstream target of mTORC1, p70S6 kinase, in a concentration and time dependent manner...
December 2016: Neuropharmacology
Daphnée Michelet, Juliette Andreu-Gallien, Alia Skhiri, Arnaud Bonnard, Yves Nivoche, Souhayl Dahmani
BACKGROUND AND AIMS: Laparoscopic pediatric surgery allows a rapid postoperative rehabilitation and hospital discharge. However, the optimal postoperative pain management preserving advantages of this surgical technique remains to be determined. This study aimed to identify factors affecting the postoperative recovery of bowel function after laparoscopic surgery in children. MATERIAL AND METHODS: A retrospective analysis of factors affecting recovery of bowel function in children and infants undergoing laparoscopic surgery between January 1, 2009 and September 30, 2009, was performed...
July 2016: Journal of Anaesthesiology, Clinical Pharmacology
Jeffery N Talbot, Laura M Geffert, Jessica E Jorvig, Ruben I Goldstein, Cienna L Nielsen, Nicholas E Wolters, Mary Ellen Amos, Caitlin A Munro, Elizabeth Dallman, Maddalena Mereu, Gianluigi Tanda, Jonathan L Katz, Martín Indarte, Jeffry D Madura, Hailey Choi, Rehana K Leak, Christopher K Surratt
Rational design of lead compounds targeting monoamine transporters (MATs) is critical to developing novel therapeutics to treat psychiatric disorders including depression and substance abuse. A 3-D dopamine transporter (DAT) computer model was used to virtually screen a commercially available small molecule library for high DAT affinity drug-like compounds. One hit, coded "MI-4", inhibited human dopamine, norepinephrine, and serotonin transporters in vitro. In vivo administration in mice induced robust, dose-dependent antidepressant-like behaviors in learned helplessness models (tail suspension and forced swim tests)...
August 26, 2016: Pharmacology, Biochemistry, and Behavior
Min Hou, Nai-Bao Zhou, Hao Li, Bao-Sheng Wang, Xiu-Qin Wang, Xing-Wu Wang, Kai-Guo Wang, Fu-Shan Xue
BACKGROUND: There is conflicting evidence regarding effects of anesthetic and analgesic drugs on immune function of cancer patients. This study was designed to observe changes of T cell subpopulations in the gastric cancer (GC) patients and to assess effects of morphine and ketamine on the CD4(+) T cells, CD8(+) T cells, and regulatory T cells (Tregs) populations obtained from the GC patients in vitro. METHODS: The peripheral blood samples from 20 GC patients and 20 healthy volunteers were obtained...
June 15, 2016: Journal of Surgical Research
Daniel Diaz-Gil, Friederike Haerter, Shane Falcinelli, Shweta Ganapati, Gaya K Hettiarachchi, Jeroen C P Simons, Ben Zhang, Stephanie D Grabitz, Ingrid Moreno Duarte, Joseph F Cotten, Katharina Eikermann-Haerter, Hao Deng, Nancy L Chamberlin, Lyle Isaacs, Volker Briken, Matthias Eikermann
BACKGROUND: Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery. METHODS: To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity...
August 2016: Anesthesiology
Mei-Fang Chen, Su-Yu Lai, Po-Cheng Kung, Yo-Cheng Lin, Hui-I Yang, Po-Yi Chen, Ingrid Y Liu, Ahai Chang Lua, Tony Jer-Fu Lee
The abuse of ketamine and amphetamine analogs is associated with incidence of hypertension and strokes involving activation of sympathetic activities. Large cerebral arteries at the base of the brain from several species receive dense sympathetic innervation which upon activation causes parasympathetic-nitrergic vasodilation with increased regional blood flow via axo-axonal interaction mechanism, serving as a protective mechanism to meet O2 demand in an acutely stressful situation. The present study was designed to examine effects of ketamine and amphetamine analogs on axo-axonal interaction-mediated neurogenic nitrergic vasodilation in porcine basilar arteries using techniques of blood-vessel myography, patch clamp and two-electrode voltage clamp, and calcium imaging...
August 15, 2016: Toxicology and Applied Pharmacology
Kristian Gaarn du Jardin, Nico Liebenberg, Heidi Kaastrup Müller, Betina Elfving, Connie Sanchez, Gregers Wegener
RATIONALE: The mechanisms mediating ketamine's antidepressant effect have only been partly resolved. Recent preclinical reports implicate serotonin (5-hydroxytryptamine; 5-HT) in the antidepressant-like action of ketamine. Vortioxetine is a multimodal-acting antidepressant that is hypothesized to exert its therapeutic activity through 5-HT reuptake inhibition and modulation of several 5-HT receptors. OBJECTIVES: The objective of this study was to evaluate the therapeutic-like profiles of S-ketamine, vortioxetine, and the serotonin reuptake inhibitor fluoxetine in response to manipulation of 5-HT tone...
July 2016: Psychopharmacology
Anne Batisse, Hélène Peyrière, Céline Eiden, Marie-Anne Courné, Samira Djezzar
The "SLAM" phenomenon is an increasingly popular practice, in Paris and London gay scene, defined by 3 characteristics: injection, sexual party and psychostimulant drugs. The French Medical Agency requested a risk assessment of "SLAM" and more broadly of the use of psychostimulants in a sexual context, by the analysis of complications related to this practice notified to the French Network of Addictovigilance Centers. All cases of complications related to "SLAM" practice, including cases of abuse or dependence, and somatic and psychiatric complications, were analysed...
April 26, 2016: Thérapie
Mauro Oddo, Ilaria Alice Crippa, Sangeeta Mehta, David Menon, Jean-Francois Payen, Fabio Silvio Taccone, Giuseppe Citerio
Daily interruption of sedative therapy and limitation of deep sedation have been shown in several randomized trials to reduce the duration of mechanical ventilation and hospital length of stay, and to improve the outcome of critically ill patients. However, patients with severe acute brain injury (ABI; including subjects with coma after traumatic brain injury, ischaemic/haemorrhagic stroke, cardiac arrest, status epilepticus) were excluded from these studies. Therefore, whether the new paradigm of minimal sedation can be translated to the neuro-ICU (NICU) is unclear...
2016: Critical Care: the Official Journal of the Critical Care Forum
Yuanqiao He, Qianxing Zou, Bingda Li, Houyang Chen, Xiaohong Du, Shiqi Weng, Tao Luo, Xuhui Zeng
Ketamine, a dissociative anesthetic, which was widely used in human and animal medicine, has become a popular recreational drug, as it can induce hallucinatory effects. Ketamine abuse can cause serious damage to many aspects of the organism, mainly reflected in the nervous system and urinary system. It has also been reported that ketamine can impair the male genital system. However, the detailed effect of ketamine on human spermatozoa remains unclear. Thus, we investigated the in vitro effects of ketamine on human sperm functions, to elucidate the underlying mechanism...
September 9, 2016: Biochemical and Biophysical Research Communications
Melanie Clarke, Sara Razmjou, Natalie Prowse, Zach Dwyer, Darcy Litteljohn, Rowan Pentz, Hymie Anisman, Shawn Hayley
Considerable recent attention has focused on the rapid antidepressant effects observed in treatment resistant patients produced by the NMDA receptor antagonist, ketamine. Surprisingly, the effects of ketamine in the context of stressor exposure, as well as the consequences of its chronic use are unclear. Thus, we assessed the impact of acute and repeated ketamine treatment together with acute [restraint or lipopolysaccharide (LPS)] or chronic (unpredictable different psychogenic challenges) stressor exposure...
April 20, 2016: Neuropharmacology
Ran Guo, Guangjian Liu, Min Du, Yu Shi, Pu Jiang, Xiaoli Liu, Lan Liu, Jianxia Liu, Ying Xu
BACKGROUND: Ketamine is a commonly used clinical anesthetic and a popular recreational drug. However, with the exception of studies about the nervous system, studies about the effect of early ketamine exposure on embryos are rare. Xenopus laevis is a commonly used vertebrate model for assessing teratogenicity. Therefore, we treated Xenopus embryos with ketamine to evaluate its teratogenicity on embryos. METHODS: Xenopus embryos were treated with ketamine from stages 8 to 21...
2016: BMC Anesthesiology
Fermín Fernández-Calderón, Claudio Vidal-Giné, José López-Guerrero, Óscar M Lozano-Rojas
BACKGROUND AND AIMS: There is a lack of instruments for measuring ketamine substance use disorders. The aims were (i) to estimate the reliability and provide evidence of validity of the Severity of Dependence Scale (SDS) in a sample of recreational users, and (ii) propose a cut-off point to determine the presence of dependence. METHODS: We conducted a web-based cross-sectional survey with recreational users who accessed webs related to recreational drug use and harm reduction...
September 2016: Addictive Behaviors
Riin Reimets, Sirli Raud, Maarja Loomets, Tanel Visnapuu, Vallo Volke, Ain Reimets, Mario Plaas, Eero Vasar
There is significant comorbidity between mood disorders and diabetes. Wolfram syndrome-related to deficient WFS1 gene function-causes diabetes and mood disorders in humans. Mice lacking the Wfs1 gene display impaired emotional behaviour and glucose metabolism. Various antidepressant drugs are used for alleviating the symptoms of mood disorders. For this study the tail suspension test and locomotor activity test were used to compare the effects of different antidepressants upon homozygous Wfs1-deficient, heterozygous Wfs1-deficient and wild-type mice...
July 15, 2016: Behavioural Brain Research
G M I Chowdhury, J Zhang, M Thomas, M Banasr, X Ma, B Pittman, L Bristow, E Schaeffer, R S Duman, D L Rothman, K L Behar, G Sanacora
Several drugs have recently been reported to induce rapid antidepressant effects in clinical trials and rodent models. Although the cellular mechanisms involved remain unclear, reports suggest that increased glutamate transmission contributes to these effects. Here, we demonstrate that the antidepressant-like efficacy of three unique drugs, with reported rapid onset antidepressant properties, is coupled with a rapid transient rise in glutamate cycling in the medial prefronal cortex (mPFC) of awake rats as measured by ex vivo (1)H-[(13)C]-nuclear magnetic resonance spectroscopy...
April 12, 2016: Molecular Psychiatry
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