Effects Of Ketamine Administration Research Articles

Effects of ketamine administration on the expression of Sox 2 in THE zebrafish CNS

Effects of ketamine administration on the expression of Sox 2 in THE zebrafish CNS

EFFECT OF KETAMINE ADMINISTRATION ON TESTICULAR FUNCTIONS IN ALBINO RATS

Ketamine, a composed mixture of (S)- and (R)-ketamine is used for anesthesia in clinical purpose since 1970. In the present study, effect of Ketamine administration on testicular functions like biochemical, gravimetrical and histological analysis has been studied. Three groups of healthy adult colony breed male albino rats having six rats maintained in each group were used for the experimental studies. The rats of groups II and III were administered Ketamine, intraperitoneally, at the dose level 1 and 3 mg/100 gm body weight respectively daily between 10:00 and 11:00 am for 21 days and group I was maintained as control. After the experimental duration, the rats were sacrificed and studied their gravimetric, biochemical and histological analyses of testis. In the results, testicular weights of the rats of group II and III showed significant reduction, histological, biochemical changes were also observed which marked cytotoxicity and inhibition of testicular functions. Histometric changes of testis diameter and surface epithelial cell height were reduced significantly. Biochemical changes are analogous to the gravimetric results. The protein and cholesterol contents are elevated significantly with the graded dose of Ketamine administration. While, in the gravimetric analysis of accessory organs like epididymis, vas deferens, seminal vesicle and prostate gland weights were decreased significantly due to the administration of Ketamine and exhibited as endocrine disruptive drug.

Administration of ketamine with the central and peripheral analgesics for induction of balanced anesthesia in the chicks

The aim of this study was to induce balanced anesthesia characterized by good hypnosis, analgesia and reducing the side effects of the drugs at the same time, so that, the effect of ketamine administration with both morphine and aspirin was studied in 90 chicks at 10-21 day-old and compare it with the positive control group that injected with ketamine alone. Ketamine injection at 7.5, 15 and 30 mg/kg, i.m. induce loss of righting reflex (anesthesia or hypnosis) in a dose dependent manner. The onset of anesthesia is decreased and its duration and recovery from anesthesia increased significantly in the groups that administered ketamine and morphine or ketamine and aspirin or ketamine, morphine and aspirin combination when compared to ketamine alone (positive control group). The less onset of anesthesia with enhanced duration and recovery from it were significantly when ketamine injected at 15 mg/kg, i.m. mixed with morphine and aspirin at 5 and 100 mg/kg, i.m., respectively in the chicks. This combination also caused a significantly increased in the analgesic effect through its significant elevation of the voltage after injection when compared with its value before injection as well as the significant increase in the delta voltage. The result of this study recommended the induction of balanced anesthesia, which characterized by good hypnosis and analgesic efficacy through administering ketamine with central (morphine) and peripheral (aspirin) analgesics.

The Effect of Ketamine Administration on Pain Control in Painful Crisis of Sickle Cell Anemia Patients during Childhood: A Retrospective Observational Study

Background: Sickle cell anemia (SCA) is a hemoglobinopathy as a result of substitution of glutamic acid with valine in the 6th position of the β globin chain. The vaso-occlusive crises of patients are often caused by pain that requires in-patient treatment. The attack rate is reported to changed between 0.5-1.0 attacks per year per patient. It could be reach up to 10% in 5% of patients. Identification of the SCA painful crisis and the determination of appropriate treatment is very important for the pain relief. Recently studies support that ketamine treatment is beneficial in patients who do not respond to traditional methods. Ketamine is a non-competitive antagonist at the NMDA receptor. We used retrospective visual analogue scale (VAS) scoring system in acute painful crisis patients and then applied ketamine and tramadol to investigate the effect of treatment and side effects and the maximum change in pain score within the first hour after drug administration retrospectively. The aim of this study is evaluate the level of ketamine effect in painful crises.Methods: Patients older than 6 years of age with acute painful crisis, defined as VAS of greater or equal to 4 were enrolled.The retrospective data was collected from electronic records and included age, sex, vital signs, changes in pain score within 1 hour, and side effects. Ketamine (0.25 mg / kg / dose) and tramadol (0.1-0.4 mg / kg / h) were administered. Patients with a pain score of <4 or a decrease of ≥3 points in VAS were considered to be responsive.Results: Ketamine group (n = 16), 6 female (37.5%), 10 male (63.5%) and the mean age was 15.4 (7-21) years. Tramadol group (n = 31) 15 female (48%), 16 male (52%) and the mean age was 15.6 (6-21) years. The age and sex groups were similar (p> 0.05). After drug administration, vital signs were observed in all patients in normal range to their age. In the tramadol and ketamine groups, the number of patients who responded at 20 minutes were 9(29%)-9(56%), 12(38%)-11(68%) (p<0.05) at 60 minutes. Sixteen patients (51.6%) responded in the 6th hour of the tramadol group, no evaluate in ketamin group. No life-threatening side effects was observed in any patient.Conclusion: In the treatment of painful crises, ketamine administration was found to be more effective than tramadol in the first hour. Due to the longer duration of the initial effect of tramadol treatment, ketamine should be considered as an option in the rapid treatment of painful crises. DisclosuresNo relevant conflicts of interest to declare.

Effect of ketamine administration, alone and in combination with E-6837, on climbing behavior.

Some types of schizophrenia have been associated with repetitive movements lacking specific purpose, also known as stereotyped behavior. Dopamine agonists (D2) and noncompetitive N-methyl-D-aspartate receptor antagonists (e.g. ketamine) have been administered in rodent models to induce stereotyped behavior that resembles some motor symptoms of schizophrenia. Recently, a relationship has been found between 5-HT6 receptors (5-HT6Rs) and dopaminergic activity. The present study evaluates the effect of ketamine (5 and 10 mg/kg), alone and in combination with the 5-HT6R agonist E-6837, on the climbing behavior of male mice. Ketamine was administered with an acute (1 day) and subchronic (5 day) scheme. Later, these doses and schemes were combined with an acute scheme of E-6837 (5 and 10 mg/kg). With both the acute and the subchronic schemes, ketamine increased climbing behavior at a dose of 10 mg/kg, and this effect was reversed by E-6837 (at 5 and 10 mg/kg). The present results suggest that there is an interaction between N-methyl-D-aspartate and 5-HT6 receptors in the regulation of climbing behavior. Further research is necessary to provide more evidence on this interaction.

Effects of ketamine administration on the phosphorylation levels of CREB and TrKB and on oxidative damage after infusion of MEK inhibitor.

Ketamine, an antagonist of N-methyl-d-aspartate (NMDA) receptors, has presented antidepressant effects in basic and clinical studies. The MAPK kinase (MEK) signaling pathway could be a target for novel antidepressant drugs and an important pathway involved in neuronal plasticity. Thus, this study evaluated the effects of the administration of ketamine on the phosphorylation of TrKB and CREB, and oxidative stress parameters in the prefrontal cortex (PFC), hippocampus, amygdala, and nucleus accumbens (NAc) rats, after the inhibition of MAPK pathway (PD184161). Male adult Wistar rats were submitted to a surgical procedure to receive a single dose of a pharmacological inhibitor of MAPK (PD184161) at a dose of (0.1μg/μl) or vehicle. Then, they were divided: 1) vehicle+saline; 2) inhibitor PD184161+saline; 3) vehicle+ketamine 15mg/kg; and 4) inhibitor PD184161+ketamine 15mg/kg. MEK inhibitor and ketamine increased the phosphorylation of the transcription factor cAMP response element-binding protein (pCREB) and neurotrophic factor/tropomyosin related kinase B receptor (pTrKB) in the PFC, and decreased pCREB in the hippocampus. The MEK inhibitor abolished ketamine's effects in the hippocampus. In the amygdala, pCREB was decreased, and pTrKB was increased after MEK inhibitor plus ketamine. Ketamine increased the thiobarbituric acid reactive species (TBARS) in the PFC, hippocampus, amygdala, and NAc; MEK inhibitor antagonized these effects. The carbonyl was increased in the PFC by both ketamine and MEK inhibitor, but inhibitor infusion plus ketamine administration reduced this effect. In the amygdala, MEK inhibitor increased carbonyl. Ketamine's effects on pCREB, pTrKB, and oxidative stress are mediated, at least in part, by a mechanism dependent of MAPK signaling inhibition.

Impact of subanesthetic doses of ketamine on AMPA-mediated responses in rats: An in vivo electrophysiological study on monoaminergic and glutamatergic neurons.

The rapid antidepressant action of a subanesthetic dose of ketamine in treatment-resistant patients represents the most striking recent breakthrough in the understanding of the antidepressant response. Evidence demonstrates tight interactions between the glutamatergic and monoaminergic systems. It is thus hypothesized that monoamine systems may play a role in the immediate/rapid effects of ketamine. In vivo electrophysiological recordings were carried in male rats following ketamine administration (10 and 25 mg/kg, i.p.) to first assess its effects on monoaminergic neuron firing. In a second series of experiments, the effects of ketamine administration on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartate receptor (NMDA)-evoked responses in hippocampus CA3 pyramidal neurons were also investigated using micro-iontophoretic applications. Although acute (~2 hours) ketamine administration did not affect the mean firing activity of dorsal raphe serotonin and ventral tegmental area dopamine neurons, it did increase that of locus coeruleus norepinephrine neurons. In the latter brain region, while ketamine also enhanced bursting activity, it did increase population activity of dopamine neurons in the ventral tegmental area. These effects of ketamine were prevented by the prior administration of the AMPA receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide. An increase in AMPA-evoked response of CA3 pyramidal neurons was also observed 30 minutes following acute ketamine administration. The present findings suggest that acute ketamine administration produces a rapid enhancement of catecholaminergic neurons firing activity through an amplification of AMPA transmission. These effects may play a crucial role in the antidepressant effects of ketamine observed shortly following its infusion in depressed patients.

Histological Study on the Protective Effect of Green Tea Extract on the Liver of Rats Exposed to Ketamine

Background: Green tea intake is accompanied with a lower incidence of cancer, cardiovascular disease, and neurodegenerative disorders; hence green tea extract is included in multivitamins and other dietary supplements. Aim of the work: Studying the effect of ketamine administration on the liver of adult male albino rats and demonstrating the possible protective role of green tea extract. Material and methods: Forty adult male albino rats were divided into four groups, ten rats each. Group I: control group. Group II: rats received green tea extract orally (50 mg/Kg/day) for five weeks. Group III: rats were injected intraperitoneally with ketamine (100 mg/kg/day) for two weeks. Group IV: rats received green tea extracts orally (50 mg/Kg/day) for three weeks, and then continued for further two weeks concomitantly with intraperitoneally injected ketamine (100 mg/kg/day). Serum levels of AST, ALT, GSH and MDA were measured. Liver sections were subjected to H & E, iNOS immunohistochemical stain, and toluidine blue stain and transmission electron microscopic examination. Followed by statistical analysis of biochemical and morphometric results. Results: In group III, serum liver enzymes and oxidative stress indicators together with positive area of iNOS immunohistochemical stain were significantly increased as compared to control. In liver sections of ketamine treated group, hepatocytes showed signs of degeneration and multiple cytoplasmic vacuoles of variable sizes with dilated blood sinusoids. At ultrastructural level, nuclei with irregular outline, dilated and discontinued RER with empty spaces within the cytoplasm of hepatocytes were recorded. Interestingly, the picture was comparable to control with concomitant use of green tea extract. Conclusion: Green tea extract has a hepato-protective effect in rats exposed to ketamine.

Administration of ketamine to neonatal SD rats causes abnormal prefrontal cortex development and mood disorders in adult

Objective To investigate the effect of ketamine administration to neonatal SD rats on prefrontal cortex development and emotional state in adult.Methods Forty postnatal day 7 (P7) SD rats were randomly assigned to receive intraperitoneal injection of 50 mg/kg ketamine (K group) or 0.25 ml saline (NS group),once every 30 min for totally 4 times.The expression of cysteinyl aspartate-specific protease-3 (Caspase-3) in the prefrontal cortex was detected by Western blotting at 6 h after the last injection,and the remaining pups were allowed to grow up with their mothers until P30.Behavioral tests were done to evaluate cognitive function and mood state on P30-P33.After behavioral tests,rats were sacrificed for Nissl staining to study the cytoarchitecture development of prefrontal cortex.Results P7 rats exposed to ket-amine caused up-regulated expression of Caspase-3 in the prefrontal cortex (n =5,P ＜ 0.05).At P30,as compared with control group,the center area of the environment [NS group:(25.9 ± 2.2) s,K group:(16.5±2.0) s,n=15,P＜0.01],sucrose intake [NS group:(77.0±2.5)％,K group:(60.0±4.3) ％,n =15,P ＜ 0.01],and the cell density in the prefrontal cortex [NS group:(1 367 ± 79) cells/mm2,K group:(1 105 ± 73) cells/mm2,n =6,P ＜ 0.05] were significandy reuced in K group.Conclusion Administration of ketamine to neonatal SD rats causes depression-and anxiety-like behaviors in adult,which may be associated with cell apoptosis by up-regulating the Caspase-3 expresion and neuronal loss in the prefrontal cortex. Key words: Ketamine; Prefrontal cortex; Mood disorder; Depression; Anxiety

The blockade of NMDA receptor ion channels by ketamine is enhanced in developing rat cortical neurons

Ketamine is a non-competitive antagonist of NMDA receptors (NMDARs) commonly used as a dissociative anesthetic in many pediatric procedures. Ketamine acts primarily by blocking NMDA ligand-gated channels. Experimental studies indicate that ketamine administration used for inducing clinically relevant anesthesia can lead to neurotoxic effects, such as apoptosis, selectively on immature brain neurons. However, the underlying mechanisms remain unclear. This study used whole-cell patch-clamp recordings in an in vitro preparation of forebrain slices to analyze pharmacologically the differences in the effects of ketamine administration on the NMDAR channel activity between immature and mature neurons. NMDAR channel activity was recorded in the form of evoked NMDAR-mediated excitatory postsynaptic currents (eEPSCs) from the forebrain of both neonatal and adult rats. Results show that ketamine inhibited eEPSCs in a dose-dependent manner in both immature and mature neurons. However, at each concentration of ketamine applied to the brain slice, a more extensive inhibition could be seen in neonatal neurons than in adult neurons. Further, the blocking effect of ketamine on eEPSCs was measured during the period of 1, 3, and 6h after ketamine washout. Inhibition of eEPSCs in immature neurons was still evident 6h after washout. In contrast, the blockade of eEPSCs in mature neurons recovered completely from the inhibition by ketamine in a time-dependent manner. These results indicate that ketamine produces a greater and longer blocking effect on NMDAR channels in immature neurons than in mature neurons. This differential effect is likely to be a critical link to the higher vulnerability to ketamine-induced neurotoxicity in neurons of the developing brain.

Ketamine administration inhibits c-Fos expression in mice retrosplenial cortex

Objective To investigate the effects of ketamine administration on expression of c-Fos and pCREB in Kunming mice retrosplenial cortex. Methods The adult male Kunming mice were randomly allocated into four groups,control,K1,K2,K3 and groups,in which normal saline and different doses of ketamine including 50,100,200 mg/kg were intraperitoneally injected at 5-day interval for successively 6 times,respectively.The expression of c-Fos and pCREB in retrosplenial cortex were detected via immunohistochemistry method.Results ① There was a basal expression of c-Fos and pCREB in retrosplenial cortex.② Chronic ketamine administration dose-dependently downregulated the expression of c-Fos in retrosplenial cortex.Compared to saline control group,ketamine with different doses decreased the c-Fos expression to 80％,43％ and 37％,and increased the expression of pCREB to 180％,195％ and 170％. Conclusions Chronic ketamine injection inhibits the expression of c-Fos expressions in retrosplenial cortex,which may be related to the upregulation of pCREB expression. Key words: c-Fos; pCREB; Phosphorylation; Forebrain

The Effect of Ketamine Administration on Nocturnal Sleep Architecture

The Effect of Ketamine Administration on Nocturnal Sleep Architecture

The Effect of Ketamine Administration on Nocturnal Sleep Architecture

The Effect of Ketamine Administration on Nocturnal Sleep Architecture

The Effect of Ketamine Administration on Nocturnal Sleep Architecture

Substantial evidence exists in the acute, rehabilitative and outpatient settings demonstrating the presence of significant sleep pattern disturbances after burn injury. Although the etiology is multifactorial and includes environmental, injury, and treatment mediators, previous clinical studies have not analyzed the critically important relationship of various medications to sleep architecture. The purpose of this investigation was to describe the after-effect of ketamine on sleep patterns in seriously ill burn patients. Forty pediatric patients with a mean TBSA burn of 50.1 ± 2.9% (range, 22-89%) and full-thickness injury of 43.2 ± 3.6% (range, 24-89%) were enrolled in this sleep study. Twenty-three of the 40 patients received ketamine on the day of polysomnography testing. Standard polysomnographic sleep variables were measured from 10:00 pm until 7:00 am. Chi-square test and t-test were used for comparison of descriptive variables between the ketamine and nonketamine groups. A logarithmic transformation was used for analysis when necessary. Ketamine administration was associated with reduced rapid eye movement (REM) sleep when compared with patients who did not receive ketamine on the day of the sleep study (P < 0.04). Both ketamine and nonketamine groups were clearly REM deficient when compared with nonburn norms. There was no relationship between ketamine use and effect on nocturnal total sleep time, number of awakenings, or percent of time awake or in stage 1, 2, or 3 + 4 sleep. In conclusion, ketamine was associated with altered sleep architecture as evidenced by a reduction in REM sleep. This finding does not seem to be clinically significant when considering the magnitude of overall REM sleep pattern disturbance observed in both the ketamine and nonketamine groups compared with nonburn norms. Further research is required to identify potential mechanisms of disturbed sleep so that appropriate interventions can be developed.

Ketamine Produces Lasting Disruptions in Encoding of Sensory Stimuli

The current study analyzed the acute, chronic, and lasting effects of ketamine administration in four inbred mouse strains (C3H/HeHsd, C57BL/6Hsd, FVB/Hsd, and DBA/2Hsd) to evaluate vulnerability to ketamine as a drug of abuse and as a model of schizophrenia. Serum half-life of ketamine was similar between all strains (approximately 13 min). Also, the ratio of brain-to-serum ketamine levels was 3:1. Examination of multiple phases of auditory processing using auditory-evoked potentials (AEPs) following acute ketamine (0, 5, and 20 mg/kg) treatment revealed C3H/HeHsd mice to be most vulnerable to ketamine-induced alterations in AEPs, whereas FVB/Hsd mice exhibited the least electrophysiological sensitivity to ketamine. Overall, the precortical P1-evoked potential component increased in amplitude and latency, whereas the cortically generated N1 and P2 components decreased in amplitude and latency following acute ketamine across all strains. Brain catecholamine analyses indicated that ketamine decreased hippocampus epinephrine levels in C3H/HeHsd but elevated hippocampus epinephrine levels in FVB/Hsd, suggesting one potential mechanism for AEP vulnerability to ketamine. Based on results of the acute study, the immediate and lasting effects of chronic low-dose ketamine on AEPs were examined among C3H/HeHsd (sensitive) and FVB/Hsd (insensitive) mice. We observed a decrement of the N1 amplitude that persisted at least 1 week after the last exposure to ketamine across both strains. This lasting deficit in information processing occurred in the absence of acute changes among the FVB/Hsd mice. Implications for both ketamine abuse and N-methyl-D-aspartate hypofunction models of schizophrenia are discussed.