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Ketamine long-term effects

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https://www.readbyqxmd.com/read/28926001/ketamine-differential-neurophysiological-dynamics-in-functional-networks-in-the-rat-brain
#1
A Ahnaou, H Huysmans, R Biermans, N V Manyakov, W H I M Drinkenburg
Recently, the N-methyl-d-aspartate-receptor (NMDAR) antagonist ketamine has emerged as a fast-onset mechanism to achieve antidepressant activity, whereas its psychomimetic, dissociative and amnestic effects have been well documented to pharmacologically model schizophrenia features in rodents. Sleep-wake architecture, neuronal oscillations and network connectivity are key mechanisms supporting brain plasticity and cognition, which are disrupted in mood disorders such as depression and schizophrenia. In rats, we investigated the dynamic effects of acute and chronic subcutaneous administration of ketamine (2...
September 19, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28840469/early-exposure-to-ketamine-impairs-axonal-pruning-in-developing-mouse-hippocampus
#2
Aleksandar Lj Obradovic, Navya Atluri, Lorenza Dalla Massara, Azra Oklopcic, Nikola S Todorovic, Gaurav Katta, Hari P Osuru, Vesna Jevtovic-Todorovic
Mounting evidence suggests that prolonged exposure to general anesthesia (GA) during brain synaptogenesis damages the immature neurons and results in long-term neurocognitive impairments. Importantly, synaptogenesis relies on timely axon pruning to select axons that participate in active neural circuit formation. This process is in part dependent on proper homeostasis of neurotrophic factors, in particular brain-derived neurotrophic factor (BDNF). We set out to examine how GA may modulate axon maintenance and pruning and focused on the role of BDNF...
August 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28828210/short-and-long-term-antidepressant-effects-of-ketamine-in-a-rat-chronic-unpredictable-stress-model
#3
Yinghong Jiang, Yiqiang Wang, Xiaoran Sun, Bo Lian, Hongwei Sun, Gang Wang, Zhongde Du, Qi Li, Lin Sun
OBJECTIVE: This research was aimed to evaluate the behaviors of short- or long-term antidepressant effects of ketamine in rats exposed to chronic unpredictable stress (CUS). BACKGROUND: Ketamine, a glutamate noncompetitive NMDA receptor antagonist, regulates excitatory amino acid functions, such as anxiety disorders and major depression, and plays an important role in synaptic plasticity and learning and memory. METHODS: After 42 days of CUS model, male rats received either a single injection of ketamine (10 mg/kg; day 43) or 15 daily injections (days 43-75)...
August 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28802882/chronic-opioid-therapy-modifies-qst-changes-following-ketamine-infusion-in-chronic-pain-patients
#4
Dermot P Maher, Yi Zhang, Shihab Ahmed, Tina Doshi, Charlene Malarick, Kristin Stabach, Jianren Mao, Lucy Chen
The long-term effects of opioids on sensitization processes are believed to be mediated through the NDMA receptor. QST changes observed following a ketamine infusion have been previously described but the effect that chronic opioids will have is not known. The results of this prospective randomized factorial trial compared the thermal QST changes observed following a 0.05 mg/kg ketamine infusion or a saline placebo in chronic pain subjects who were either opioid-naïve or were chronically using opioids for chronic non-cancer pain are presented...
August 9, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28798343/isoflurane-produces-antidepressant-effects-and-induces-trkb-signaling-in-rodents
#5
Hanna Antila, Maria Ryazantseva, Dina Popova, Pia Sipilä, Ramon Guirado, Samuel Kohtala, Ipek Yalcin, Jesse Lindholm, Liisa Vesa, Vinicius Sato, Joshua Cordeira, Henri Autio, Mikhail Kislin, Maribel Rios, Sâmia Joca, Plinio Casarotto, Leonard Khiroug, Sari Lauri, Tomi Taira, Eero Castrén, Tomi Rantamäki
A brief burst-suppressing isoflurane anesthesia has been shown to rapidly alleviate symptoms of depression in a subset of patients, but the neurobiological basis of these observations remains obscure. We show that a single isoflurane anesthesia produces antidepressant-like behavioural effects in the learned helplessness paradigm and regulates molecular events implicated in the mechanism of action of rapid-acting antidepressant ketamine: activation of brain-derived neurotrophic factor (BDNF) receptor TrkB, facilitation of mammalian target of rapamycin (mTOR) signaling pathway and inhibition of glycogen synthase kinase 3β (GSK3β)...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28758582/potential-novel-treatments-for-bipolar-depression-ketamine-fatty-acids-anti-inflammatory-agents-and-probiotics
#6
G H Vázquez, S Camino, L Tondo, Ross J Baldessarini
BACKGROUND: Treatments for depression in bipolar disorder (BD) are far less well developed than for unipolar major depressive disorder. Several innovative and experimental approaches have been emerging recently, including use of the dissociative anesthetic ketamine and other antagonists of central NMDA glutamate receptors, as well as unsaturated fatty acids, anti-inflammatory agents, and possibly probiotic methods. METHODS: We reviewed relevant reports from the past decade...
July 28, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28757132/side-effects-associated-with-ketamine-use-in-depression-a-systematic-review
#7
REVIEW
Brooke Short, Joanna Fong, Veronica Galvez, William Shelker, Colleen K Loo
This is the first systematic review of the safety of ketamine in the treatment of depression after single and repeated doses. We searched MEDLINE, PubMed, PsycINFO, and Cochrane Databases and identified 288 articles, 60 of which met the inclusion criteria. After acute dosing, psychiatric, psychotomimetic, cardiovascular, neurological, and other side-effects were more frequently reported after ketamine treatment than after placebo in patients with depresssion. Our findings suggest a selective reporting bias with limited assessment of long-term use and safety and after repeated dosing, despite these being reported in other patient groups exposed to ketamine (eg, those with chronic pain) and in recreational users...
July 27, 2017: Lancet Psychiatry
https://www.readbyqxmd.com/read/28735534/investigation-and-application-of-a-new-passive-sampling-technique-for-in-situ-monitoring-of-illicit-drugs-in-waste-waters-and-rivers
#8
Changsheng Guo, Tingting Zhang, Song Hou, Jiapei Lv, Yuan Zhang, Fengchang Wu, Zhendong Hua, Wei Meng, Hao Zhang, Jian Xu
Illicit drugs constitute a class of emerging contaminants that has been drawing significant concern due to its potent pharmacological and biological activities. In this study, an in situ passive sampling approach that uses diffusive gradients in thin films (DGT) was successfully tested for measuring ketamine (KET), methamphetamine (METH), and amphetamine (AMP) in water. The diffusion coefficients of KET, METH, and AMP in diffusive gel were (8.13 ± 0.12) × 10(-6), (8.55 ± 0.14) × 10(-6), and (7.72 ± 0.18) × 10(-6) cm(2) s(-1) at 22 °C, respectively...
August 4, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28579941/chronic-ketamine-exposure-causes-white-matter-microstructural-abnormalities-in-adolescent-cynomolgus-monkeys
#9
Qi Li, Lin Shi, Gang Lu, Hong-Luan Yu, Fu-Ki Yeung, Nai-Kei Wong, Lin Sun, Kai Liu, David Yew, Fang Pan, De-Feng Wang, Pak C Sham
Acute and repeated exposures to ketamine mimic aspects of positive, negative, and cognitive symptoms of schizophrenia in humans. Recent studies by our group and others have shown that chronicity of ketamine use may be a key element for establishing a more valid model of cognitive symptoms of schizophrenia. However, current understanding on the long-term consequences of ketamine exposure on brain circuits has remained incomplete, particularly with regard to microstructural changes of white matter tracts that underpin the neuropathology of schizophrenia...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28474988/premedication-with-fentanyl-midazolam-improves-sevoflurane-anesthesia-for-surgical-intervention-in-laboratory-mice
#10
Miriam Lipiski, Margarete Arras, Paulin Jirkof, Nikola Cesarovic
Balanced anesthesia allows for a reduced dosage of each component, while inducing general anesthesia of sufficient depth with potentially fewer side effects. Here, we compare two anesthetic protocols combining sevoflurane anesthesia with pre-medication (ketamine [K] or fentanyl-midazolam [FM]) to a sevoflurane monoanesthesia (S) concerning their ability to provide reliable anesthesia suitable for moderate surgery in laboratory mice. Twenty-one female C57BL/6J mice assigned randomly to one of three protocols underwent a 50-min anesthesia and a sham embryo transfer...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28473755/the-combination-of-long-term-ketamine-and-extinction-training-contributes-to-fear-erasure-by-bdnf-methylation
#11
Ling-Sha Ju, Jiao-Jiao Yang, Lei Lei, Jiang-Yan Xia, Dan Luo, Mu-Huo Ji, Anatoly E Martynyuk, Jian-Jun Yang
A combination of antidepressant drugs and psychotherapy exhibits more promising efficacy in treating fear disorders than either treatment alone, but underlying mechanisms of such treatments remain largely unknown. Here we investigated the role of DNA methylation of the brain-derived neurotrophic factor (Bdnf) gene in the therapeutic effects of ketamine in combination with extinction training in a mouse model of post-traumatic stress disorder (PTSD) induced by inescapable electric foot shocks (IFS). Male mice received ketamine for 22 consecutive days starting 1 h after the IFS (long-term ketamine treatment) or 2 h prior to the extinction training on days 15 and 16 after the IFS (short-term ketamine treatment)...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28472198/clozapine-counteracts-a-ketamine-induced-depression-of-hippocampal-prefrontal-neuroplasticity-and-alters-signaling-pathway-phosphorylation
#12
Marion Rame, Dorian Caudal, Esther Schenker, Per Svenningsson, Michael Spedding, Thérèse M Jay, Bill P Godsil
Single sub-anesthetic doses of ketamine can exacerbate the symptoms of patients diagnosed with schizophrenia, yet similar ketamine treatments rapidly reduce depressive symptoms in major depression. Acute doses of the atypical antipsychotic drug clozapine have also been shown to counteract ketamine-induced psychotic effects. In the interest of understanding whether these drug effects could be modeled with alterations in neuroplasticity, we examined the impact of acutely-administered ketamine and clozapine on in vivo long-term potentiation (LTP) in the rat's hippocampus-to-prefrontal cortex (H-PFC) pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28461248/simultaneous-triple-therapy-for-the-treatment-of-status-epilepticus
#13
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...
August 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28461010/effects-of-ketamine-dexmedetomidine-and-propofol-anesthesia-on-emotional-memory-consolidation-in-rats-consequences-for-the-development-of-post-traumatic-stress-disorder
#14
Maria Morena, Andrea Berardi, Andrea Peloso, Daniela Valeri, Maura Palmery, Viviana Trezza, Gustav Schelling, Patrizia Campolongo
Intensive Care Unit (ICU) or emergency care patients, exposed to traumatic events, are at increased risk for Post-Traumatic Stress Disorder (PTSD) development. Commonly used sedative/anesthetic agents can interfere with the mechanisms of memory formation, exacerbating or attenuating the memory for the traumatic event, and subsequently promote or reduce the risk of PTSD development. Here, we evaluated the effects of ketamine, dexmedetomidine and propofol on fear memory consolidation and subsequent cognitive and emotional alterations related to traumatic stress exposure...
June 30, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28438647/effects-of-bms-902483-an-%C3%AE-7-nicotinic-acetylcholine-receptor-partial-agonist-on-cognition-and-sensory-gating-in-relation-to-receptor-occupancy-in-rodents
#15
Rick L Pieschl, Regina Miller, Kelli M Jones, Debra J Post-Munson, Ping Chen, Kimberly Newberry, Yulia Benitex, Thaddeus Molski, Daniel Morgan, Ivar M McDonald, John E Macor, Richard E Olson, Yukiko Asaka, Siva Digavalli, Amy Easton, James Herrington, Ryan S Westphal, Nicholas J Lodge, Robert Zaczek, Linda J Bristow, Yu-Wen Li
The α7 nicotinic acetylcholine receptor is thought to play an important role in human cognition. Here we describe the in vivo effects of BMS-902483, a selective potent α7 nicotinic acetylcholine receptor partial agonist, in relationship to α7 nicotinic acetylcholine receptor occupancy. BMS-902483 has low nanomolar affinity for rat and human α7 nicotinic acetylcholine receptors and elicits currents in cells expressing human or rat α7 nicotinic acetylcholine receptors that are about 60% of the maximal acetylcholine response...
July 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28415680/long-term-neurocognitive-dysfunction-in-offspring-via-ngf-erk-creb-signaling-pathway-caused-by-ketamine-exposure-during-the-second-trimester-of-pregnancy-in-rats
#16
Yanan Li, Xinran Li, Cen Guo, Lina Li, Yuxin Wang, Yiming Zhang, Yu Chen, Wenhan Liu, Li Gao
Early life exposure to ketamine caused neurohistopathologic changes and persistent cognitive dysfunction. For this study, a pregnant rat model was developed to investigate neurocognitive effects in the offspring, following ketamine exposure during the second trimester. Pregnant rats on gestational day 14 (equal to midtrimester pregnancy in humans), intravenously received 200 mg/kg ketamine for 3 h. Their behavior was tested (Morris water maze, odor recognition test, and fear conditioning) at postnatal days (P25-30)...
May 9, 2017: Oncotarget
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
#17
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/28363076/continuous-intravenous-infusion-anesthesia-with-medetomidine-ketamine-and-midazolam-after-induction-with-a-combination-of-etorphine-medetomidine-and-midazolam-or-with-medetomidine-ketamine-and-butorphanol-in-impala-aepyceros-melampus
#18
Christina A Gerlach, Maya S Kummrow, Leith C Meyer, Gareth E Zeiler, George F Stegmann, Roxanne K Buck, Geoffrey T Fosgate, Sabine B Kästner
In order to develop a long-term anesthesia for flighty antelope species in field situations, two different protocols for induction and maintenance with an intravenous infusion were evaluated in wild-caught impala ( Aepyceros melampus ). Ten adult female impala were induced with two induction protocols: one consisted of 0.2 mg/kg medetomidine, 4 mg/kg ketamine, and 0.15 mg/kg butorphanol (MKB) and one consisted of 0.375 mg/kg etorphine, 0.2 mg/kg medetomidine, and 0.2 mg/kg midazolam (EMM). In both treatments, anesthesia was maintained with a continuous intravenous infusion (CII) at an initial dose rate of 1...
March 2017: Journal of Zoo and Wildlife Medicine: Official Publication of the American Association of Zoo Veterinarians
https://www.readbyqxmd.com/read/28339431/perioperative-ketamine-administration-for-thoracotomy-pain
#19
REVIEW
Daniel W Moyse, Alan D Kaye, James H Diaz, Muhammad Y Qadri, David Lindsay, Srinivas Pyati
BACKGROUND: Of all the postsurgical pain conditions, thoracotomy pain poses a particular therapeutic challenge in terms of its prevalence, severity, and ensuing postoperative morbidity. Multiple pain generators contribute to the severity of post-thoracotomy pain, and therefore a multimodal analgesic therapy is considered to be a necessary strategy. Along with opioids, thoracic epidural analgesia, and paravertebral blocks, N-Methyl-D-Aspartate (NMDA) receptor antagonists such as ketamine have been used as adjuvants to improve analgesia...
March 2017: Pain Physician
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
#20
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
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