Injection Of Ketamine Research Articles

Anti-diabetic Effects of Two Species of Eryngium on Streptozotocin-induced Diabetic Mice

Background: Eryngium is a genus with 274 species, which belongs to the Umbelliferae family. The nine species of this genus are endemic to Iran. The existence of terpenoids, saponins, flavonoids, and steroid components in most Eryngium species is the reason behind their anti-inflammatory, anti-cancer, and especially, anti-diabetic effects among the well-known medicinal plants. Objectives: This study aimed to evaluate the effects of anti-diabetic features of Eryngium thyrsoideum and caucasicum on streptozotocin (STZ)-induced diabetic mice. Methods: The extract of the plants’ dried samples was prepared by using 70% ethanol solvent and adopting the maceration method. The mice were divided into eight groups, and the mice with a high blood glucose of more than 200 mg/dL were assigned to diabetic groups. Diabetic animals received different doses of the extract orally or through intraperitoneal (IP) injection for eighteen days. The animals were anesthetized by IP injection of ketamine and xylazine, and serum samples were isolated. Results: The results showed that hydroalcoholic extract of E. thyrsoideum significantly reduced the blood sugar level in diabetic groups receiving the extract (oral and IP) in low (100 mg/kg) and high (300 mg/kg) doses. Overall, oral glucose tolerance decreased significantly after two hours. Coincidental management of STZ and 300 mg/kg of the extract consumed orally reduced the blood sugar level remarkably. Serum malondialdehyde (MDA) and serum insulin levels significantly decreased and increased, respectively, in the diabetic groups receiving low and high doses (oral and IP) of the E. thyrsoideum extract. In the case of E. caucasicum, no significant effect in terms of reducing blood sugar and other factors was observed. Conclusions: In sum, receiving 100 mg/kg and 300 mg/kg of hydroalcoholic extract (oral and IP) decreased the blood sugar level, while receiving oral glucose tolerance, serum MDA, and serum insulin caused a significant increase.

Ketamine-induced hippocampal functional connectivity alterations associated with clinical remission in major depression

ObjectiveHippocampal functional connectivity (FC) alterations, which may happen following ketamine treatment, play a key role in major depression remission. This study aims to investigate the resting-state FC changes of the hippocampus associated with clinical remission after repeated ketamine infusions. MethodsForty-four major depressive patients received six intravenous ketamine (0.5 mg/kg) infusions in 12 days. The FC change of the hippocampus subregions following ketamine treatment was compared between remitters (MADRS score ≤ 10 post-treatment) and nonremitters. We also investigated whether baseline hippocampus FC predicted the antidepressant efficiency of ketamine using Receiver Operating Characteristic Curve analyses. ResultsThirty-nine patients were included in the analysis. There were significant differences in change of left rostral hippocampus FC with the right angular gyrus (the key node of the default mode network, DMN), left inferior parietal cortex and the right superior parietal cortex (parts of the dorsal attention network, dAN) between remitters and nonremitters following ketamine treatment. Specifically, while the remitters showed significantly less negative hippocampus FC than the nonremitters at baseline, the FC significantly decreased in remitters but increased in nonremitters after ketamine injections. Moreover, baseline hippocampus FC with the above three regions predicted the antidepressant effect of ketamine, with the highest predictive strength identified in the hippocampus-right angular gyrus FC (Area-Under-Curve = 0.8179, p < 0.05). ConclusionKetamine treat depression by modulating the left rostral hippocampus resting-state FC with the DMN and dAN. The FC between the hippocampus and parts of the DMN and dAN may show promising potential in predicting remission after ketamine treatment in MDD.

COMPARISON OF INTRAMUSCULAR VERSUS INTRAVENOUS KETAMINE FOR SEDATION IN CHILDREN UNDERGOING MAGNETIC RESONANCE IMAGING EXAMINATION.

The aim: To compare efficacy of intramuscular (IM) versus intravenous (IV) ketamine for sedation in children undergoing brain MRI scanning in children. Materials and methods: Children who required elective brain MRI were selected for this study. They were randomly divided into two groups; group I received 1.5 mg/kg IV Ketamine and group II received 4 mg/kg IM ketamine. In each group supplementary 0.1 mg/kg midazolam intravenously before positioning on MRI table was given. Patients were monitored for pulse rate, SPO2, and respiratory wave. Results: Children who received IM ketamine had significantly shorter scan time and a greater success rate of sedation with first dose than the IV group. The proportions of scan interruption and scan repeat were significantly higher among the IV group than in the IM group. The scan time was longer among the IV group than in the IM group with significantly more scan interruption and repeat. Satisfaction with sedation as expressed by the technicians was significantly more in the IM group than in IV group (98.1% vs. 80.8%, P= 0.004). Conclusions: Intramuscular ketamine injection was predicted to have a better sedative success rate and takes less time to complete than intravenous admin¬istration. This makes IM ketamine more appealing in certain conditions.

Anesthetic and clinical assessments of I/V propofol versus ketamine in Dogs premedicated with diazepam

The present anesthetic investigation was aimed to evaluate anesthetic clinico-physiological and hematobiochemical effects in addition to the anesthetic properties of propofol or ketamine premedicated with diazepam . For this purpose, 12 apparently healthy dogs were randomly divided into Two groups: A and B. All dogs were premedicated with Diazepam (0.2mg/kg Bwt/IM) then intravenous anesthesia was induced in group A with propofol intravenous (1mg/kg Bwt) ,while group B with ketamine intravenous (5 mg/kg Bwt). Blood samples were collected from the Two groups 15 minutes before anesthesia induction, then at (15, 30, 45 and 60) minutes after treatments for the hemato-biochemical evaluation, and for clinico-physiological observations. A slight alteration in some physiological parameters and hemato-biochemical values was observed after anesthesia induction, but it still safe to induce general anesthesia in dogs. in conclusion, the present anesthetic investigation showed the longest period of anesthesia with complete muscle relaxation following intravenous ketamine injection than propofol in premedicated dogs with diazepam.

PECULIARITIES OF THE STRUCTURAL AND FUNCTIONAL REARRANGEMENT OF THE PARENCHYMA OF THE TESTES OF RATS WITH DOSED STENOSIS OF THE AORTO-ILIAC SEGMENT

Relevance. Abdominal ischemic disease is a general term that characterizes various clinical syndromes of damage to the organs of the digestive system when blood flow is disturbed in the abdominal part of the aorta and its branches, as a result of which there is a disparity of the blood supply of internal organs to their energy needs with the subsequent development of chronic ischemia and necrosis of cells and tissue.&#x0D; Objective. To establish the characteristic features of the dynamics of the remodeling of the blood vessel of the testicles of rats with dosed stenosis of the aorto-iliac segment.&#x0D; Materials and methods. The experiment was conducted on 48 white outbred sexually mature male rats with an average age of 3 months and a weight of 180-200 g. All animals were divided into two groups: experimental group consisted of 36 animals with simulated dosage stenosis of the aorto-iliac segment and control group (12 subjects). All operative manipulations were performed in compliance with the rules of asepsis and antisepsis. Preliminary anesthetization of the animals was carried out with the intramuscular injections of ketamine (50 mg/ml) in terms of 0.083 mg/g of body weight. After performing a laparotomy through a midsection along the white line of the abdominal wall, the abdominal aorta was isolated and compressed by 1/3 of its diameter by applying a silk ligature. The degree of narrowing was controlled using a metal probe with a cone-shaped tip according to the already known method. On the 1st, 3rd, 7th, and 14th day, the animals were taken out of the experiment and an organometric assessment of the condition of the testicles was carried out with the determination of the following parameters: the weight of the organ was determined using a torsion weight VT-500, the length and width were measured using a caliper. After that, pieces of testicular tissue were taken and fixed in a 10% solution of neutral formalin and 96% ethyl alcohol. The obtained paraffin sections with a thickness of 5-7 μm were stained with hematoxylin and eosin, and microscopic examination of a series of histological sections was carried out.&#x0D; Results. A day after the simulation of experimental stenosis of the aorto-iliac segment, a microscopic examination of the structures of the testicle revealed significant swelling of the stroma of the organ. The interstitial tissue was unevenly located between the tortuous seminiferous tubules, the lumen between which was slightly expanded. At the same time, the internal structure of the tubules remained preserved, layers of spermatogenic cells at different stages of maturation were clearly differentiated in them.&#x0D; On the third day of observation, previously identified signs of disorders of organ blood circulation in the testicles continued to increase. The swelling of the testicular interstitial tissue slightly decreased, but it was accompanied by changes in the structure of the cells of the spermatogenic epithelium, the manifestation of which was the detachment of spermatogonia from the basal membrane of the tubules and the expansion of the spaces between the rows of spermatogenic cells. The walls of the small arteries and arterioles were still significantly thickened.&#x0D; On the 7th day of observation, against the background of a significant decrease in the swelling of the space between the tortuous seminiferous tubules, dystrophic changes in the testicular tissue began to increase.&#x0D; On the 14th day of observation, even more expressed signs of organ hemodynamics violation were observed, and as a result, deviations of the trophism of testicles of experimental animals. Manifestation of such changes were prominent arterial and venous plethora. Large-caliber arteries were significantly filled with blood, and as a result, small and medium-caliber arteries, especially arterioles, had thickened walls and a markedly narrowed lumen.&#x0D; Conclusion. With dosed stenosis of the aorto-iliac segment, significant disorders of central hemodynamics occur, which are characteristic of occlusive diseases of the aorta and its branches.&#x0D; As a result, in the testes of sexually mature male rats, dystrophic changes in the cells of the spermatogenic epithelium occur and the functional activity of the organ decreases, which can form the basis for the development of infertility.

Ketamine Inhalation Alters Behavior and Lower Urinary Tract Function in Mice.

We aimed to evaluate behavioral and lower urinary tract changes in mice using a novel ketamine inhalation model mimicking human ketamine abusers and compare the results to those obtained using a ketamine intraperitoneal injection model. C57BL/6N mice were placed in a transparent acrylic observation cage connected to an ultrasonic nebulizer producing ketamine (KI) or saline (SI) fog. The mice were given KI or SI fog twice a week for three months. In another experiment arm, the mice were given intraperitoneal ketamine injections (KP) or saline injections (SP) twice a week for three months. The presence of urine ketamine (&gt;100 ng/mL) was determined using a quick test kit. Locomotor activity was recorded by video using the open field test. Lower urinary tract function was assessed using urine spots, cystometry and histology. KI and KP mice crossed the center more frequently and traveled farther than SI and SP mice. Only KI mice, however, demonstrated popcorn-like jumping, and frequent center crossing. Detrusor overactivity, reduced cystometric bladder capacity, and denuded mucosa were observed in both KI and KP mice. Ketamine inhalation induces behavioral and lower urinary tract changes in mice that are comparable to intraperitoneal ketamine injections.

Immunopathological Assessment of Hydatid Cyst and Cysticercus Tenuicollis Sonicated Protoscoilces Antigens in Mice

The present study was designed to investigate the cross-protection (protective immunity) between Hydatid cyst and Bladder worm and evaluate the immunologic response of both humerol and cellular immunity in mice. To achieve these goals, 120 mice were used and equally divided into four groups immunized subcutaneously with 2 doses of antigen at the first and 14 days of the experiment. Mice in the first group (n=30) were immunized with 0.3 ml of hydatid cyst sonicated protoscolex antigen. Those in the second group (n=30) were immunized s/c with 0.3 ml of Cysticercus tenuicollis sonicated protscolex antigen. The third group (n=30) was immunized with 0.3 ml of both antigens (0.15 + 0.15), and the fourth group was a control group in which the mice were intraperitoneally injected with 0.2 ml of phosphate buffer solution. At the end of the experiment (30 days), blood samples were taken from the hearts of mice in all groups after being anesthetized by intramuscular injection of Ketamine 60 mg/kg, and Xylazine 12 mg/kg for the assessment of mouse Interleukin-12, IgG, and tumor necrosis alpha levels. The skin test results 24 hours (day 28) post-immunization showed an increase in the skin thickness against both antigens in the treatments, compared to the control. However, there was a decrease at 48 hours (day 29) post-examination in all groups. The results of TNFα titer showed higher titer in the third group, compared to the first, second, and fourth groups. Interleukin 12 concentration showed a higher titer in the third group than in the first, second, and fourth groups. The IgG concentration showed higher titer in the third group compared to the first, second, and fourth groups. In conclusion, immunopathological studies have shown that Ags used in the study, induce humoral and cellular immunity, compared to each Ag alone, and the mixed antigens were much more immunogenic. This cross-reactivity and synergistic interactions between the two parasites may be the cause of their antigenic activities.

Effect of Atropine Sulphate on Laryngeal Accessibility and Visibility for Swine Intubation

Background: Animal intubation is necessary in painful surgery procedures in order to maintain general anaesthesia and analgesia. In swine, orotracheal intubation is difficult or impossible; all possible measures to improve it need to be explored. Methods: Two groups of a total of 20 clinically healthy local mixed breed (Sus scrofa domesticus) premedicated swine underwent intubation. The animals were randomly divided into two groups, one using atropine sulphate (A) and one using saline solution (N), prior to endotracheal intubation. Premedication started with intramuscular injection of xylazine, ketamine and fentanyl. Intubation was performed after induction with thiopental sodium administered intravenously with atropine sulphate or saline solution. Larynxes were photographed and filmed and coded images and videos were sent to investigators for evaluation. Result: In this study, a negative effect of atropine sulphate on the laryngeal visibility, opening and accessibility in local mixed breed anesthetized pigs was identified.

Combined fascial plane blocks as the sole regional anesthesia technique for breast surgery in high-risk patients.

The quest for an effective regional anaesthesia technique in breast surgery has always been eluded by its apparent complexity. Various techniques had been described as anaesthetic techniques for breast cancer surgeries. Fascial plane blocks had been used as analgesic techniques for this procedure. We describe a case series of 12 patients who were given a combination of erector spinae plane block (ESP), Pectoralis I (Pecs I) and serratus anterior plane (SAP) block as sole anaesthetic technique with high risk surgical morbidity. Two patients had discomfort during retraction of axillary apex towards the end of surgery, and one patient had discomfort during medial parasternal incision, which needed a single bolus of low dose ketamine injection. Combined fascial plane blocks could be effectively utilized as a sole regional anesthesia modality for breast cancer surgeries with mild sedation.

Analyzing Turning Behavior after Repeated Lithium, Ketamine, or NaCl Injection and Chronic Stress Exposure in Mice

A single chronic stress is often considered a potential reinforcer in psychiatric disorders. Lithium and ketamine both seem to ameliorate the consequences of stress. Here, male mice were either injected with lithium carbonate (LiCl), ketamine hydrochloride (KET), or sodium chloride (NaCl; controls) over nine consecutive days. Treatment was followed by 2 h of restraint stress over the first seven days. On the 9th day, 2 h after injection, all animals were tested in the open field, and novel object tests and behavior were analyzed using the toolbox ‘DeepLabCut’. To exclude an effect of generally altered locomotion activity on turning behavior, further parameters were assessed. Treatment before chronic stress exposure did not influence the total number of turns, nor the direction of turning behavior in the open field and the novel object test. Additionally, general locomotion did not differ. However, mice treated with LiCl showed a stronger turning bias (i.e., larger absolute lateralization quotients) in the novel object test when compared to mice treated with KET. This study underlines the potential of investigating turning behavior as a sensitive and reliable marker of stress reaction. Additionally, analyzing behavioral asymmetries in the context of psychopharmacological treatment can render new insights.

Benefits of Implementing an Enhanced Recovery After Surgery Protocol in Ambulatory Surgery.

Enhanced recovery after surgery (ERAS) protocols in orthopaedic surgery have garnered significant focus due to their ability to control pain adequately in the immediate postoperative window, allowing for earlier mobilization, shorter hospital stays, and fewer complications. Virginia Commonwealth University created a multimodal pain management approach in which patients receive a preoperative femoral nerve block followed by periarticular intraoperative local injection anesthesia consisting of bupivacaine, ketamine, and ketorolac. We hypothesized that implementation of the ERAS protocol will decrease postoperative pain scores, decrease recovery time in the postanesthesia care unit (PACU), and decrease opioid use in anterior cruciate ligament (ACL) reconstruction. Cohort study; Level of evidence, 3. Two patient cohorts were involved: before ERAS implementation (pre-ERAS) and after (post-ERAS). Patients with ACL reconstruction only and patients with ACL reconstruction with meniscal repair were analyzed separately. Post-ERAS patients received an intraoperative periarticular injection of bupivacaine, ketamine, and ketorolac and a postoperative multimodal pain regimen. Outcomes included time spent in the PACU, short-term and long-term opioid consumption, and pain score at discharge from the PACU. Compared with pre-ERAS patients, post-ERAS patients had decreased pain (2.1 vs 0.84 out of 10, respectively), spent less time in the PACU (79.4 vs 62.8 minutes, respectively), and had less opioid consumption in the immediate postoperative period (4.55 vs 2.26 total morphine milligram equivalents [MMEs], respectively) (P < .001 for all). After ERAS implementation, long-term MME use decreased from 410 to 321 between 0 and 2 weeks postoperatively, 92.6 to 1.69 between 2 and 6 weeks, and 494.5 to 323 between 0 and 6 weeks (P < .001 for all). All domains showed significant improvements for both the ACL and the ACL plus meniscal repair cohorts, with the exception of pain at discharge in the ACL plus meniscal repair group. The study findings suggest that an enhanced recovery pathways protocol that includes a standardized intraoperative periarticular bupivacaine, ketamine, and ketorolac injection improves pain scores in the immediate postoperative window, decreases opioid consumption, and reduces recovery time in the PACU for patients undergoing ACL reconstruction.

Ketamine as a sole anaesthetic agent in short surgical procedures

Background: Present clinical study was conducted to evaluate the features of ketamine hydrochloride such as rapid induction, profound analgesia and minimal cardiovascular and respiratory depression with good airway maintenance. Aim: This study has been undertaken to prove the usefulness of ketamine in the present day anaesthetic practice as a sole anaesthetic agent for short surgical procedures and evaluate the features of ketamine hydrochloride such as: 1) Rapid induction; 2) Profound analgesia; 3) Minimal cardiovascular and respiratory depression with good airway maintenance. Methods: Study was conducted on 100 patients of either sex of different age group for various short surgical procedures. All patients were pre-medicated with Inj. Atropine 0.02mg/kg and Inj. Diazepam 0.2 mg/kg IV. Following this Inj. Ketamine 2mg/kg was given intravenously. During the course of anaesthesia patient was observed for the time of onset, duration of action, hemodynamic parameters, respiration, recovery from anaesthesia and certain side effects. Results: The onset of anaesthesia after intravenous injection of ketamine was within 20-54 sec [Mean 34.3+/- 8.7]. Ketamine as a sole anaesthetic agent in short surgical procedures-a clinical studyof effect of initial dose was between 9-20 min [Mean 16.9+/- 2.9].

Individual differences in the positive outcome from adolescent ketamine treatment in a female mouse model of anorexia nervosa involve drebrin A at excitatory synapses of the medial prefrontal cortex.

Anorexia nervosa (AN) is a mental illness with the highest rates of mortality and relapse, and no approved pharmacological treatment. Using an animal model of AN, called activity-based anorexia (ABA), we showed earlier that a single intraperitoneal injection of ketamine at a dose of 30 mg/kg (30mgKET), but not 3 mg/kg (3mgKET), has a long-lasting effect upon adolescent females of ameliorating anorexia-like symptoms through the following changes: enhanced food consumption and body weight; reduced running and anxiety-like behavior. However, there were also individual differences in the drug's efficacy. We hypothesized that individual differences in ketamine's ameliorative effects involve drebrin A, an F-actin-binding protein known to be required for the activity-dependent trafficking of NMDA receptors (NMDARs). We tested this hypothesis by electron microscopic quantifications of drebrin A immunoreactivity at excitatory synapses of pyramidal neurons (PN) and GABAergic interneurons (GABA-IN) in deep layer 1 of prefrontal cortex (PFC) of these mice. Results reveal that (1) the areal density of excitatory synapses on GABA-IN is greater for the 30mgKET group than the 3mgKET group; (2) the proportion of drebrin A+ excitatory synapses is greater for both PN and GABA-IN of 30mgKET than 3mgKET group. Correlation analyses with behavioral measurements revealed that (3) 30mgKET's protection is associated with reduced levels of drebrin A in the cytoplasm of GABA-IN and higher levels at extrasynaptic membranous sites of PN and GABA-IN; (5) altogether pointing to 30mgKET-induced homeostatic plasticity that engages drebrin A at excitatory synapses of both PN and GABA-IN.

The effect of ketamine on eye movement characteristics during free-viewing of natural images in common marmosets.

Various eye movement abnormalities and impairments in visual information processing have been reported in patients with schizophrenia. Therefore, dysfunction of saccadic eye movements is a potential biological marker for schizophrenia. In the present study, we used a pharmacological model of schizophrenia symptoms in marmosets and compared the eye movement characteristics of marmosets during free-viewing, using an image set identical to those used for human studies. It contains natural and complex images that were randomly presented for 8 s. As a pharmacological model of schizophrenia symptoms, a subanesthetic dose of ketamine was injected intramuscularly for transient and reversible manipulation. Eye movements were recorded and compared under a ketamine condition and a saline condition as a control. The results showed that ketamine affected eye movement characteristics during free-viewing. Saccades amplitude and scanpath length were significantly reduced in the ketamine condition. In addition, the duration of saccades was longer under the ketamine condition than under the saline condition. A similar tendency was observed for the duration of fixations. The number of saccades and fixations tended to decrease in the ketamine condition. The peak saccades velocity also decreased after ketamine injection whereas there was no difference in the main sequence relationship between saccades amplitude and peak velocity. These results suggest that ketamine affected visual exploration but did not affect the oculomotor aspect of saccades in marmosets, consistent with studies in patients with schizophrenia. Therefore, we conclude that the subanesthetic dose of ketamine is a promising pharmacological model of schizophrenia symptoms in common marmosets and can be used in combination with free-viewing paradigms to establish “translatable markers” for schizophrenia in primates.

The functional connectivity of the middle frontal cortex predicts ketamine's outcome in major depressive disorder.

BackgroundKetamine, a robust antidepressant, has promising potential in the treatment of major depressive disorder (MDD). However, it does not work for all MDD patients, and the mechanism underlying its anti-depressive effects is unclear. Researchers have explored the mechanisms of ketamine action in MDD patients through MRI, a technique that measures brain activity intuitively. Notably, many MRI results were inconsistent because they selected different brain regions as seeds, particularly with respect to functional connectivity (FC) analysis. To eliminate the influence of prior seeds as much as possible, we used the significantly different results in degree centrality (DC) analysis as seeds to explore the FC changes in MDD patients to identify an imaging biomarker of ketamine’s effect.MethodsForty-four MDD patients and 45 healthy controls (HCs) were included in the study. Patients, aged 18–65, received six intravenous ketamine injections over 12 days. Depressive symptoms were estimated and MRI scans were performed at baseline and the day after the sixth infusion. We estimated FC differences between responders, non-responders and HCs using the region that showed significant differences between responders and non-responders in DC analysis as the seed. The correlation between the MADRS changes and zFC values was performed, and the potential of zFC values to be a neuroimaging biomarker was explored using the receiver operating characteristic curve.ResultCompared with non-responders, responders had significantly decreased DC values in the right middle frontal gyrus (MFG). In the analysis of FC using the region that showed significant differences in DC as a seed, there was a significant difference in the region of the right supplementary motor area (SMA) among responders, non-responders, and HCs. This region also overlapped with the bilateral median cingulate gyrus. In post hoc analysis, responders had higher FC than non-responders and HCs, and non-responders had lower FC than HCs. Importantly, the FC between the MFG and SMA (overlapping bilateral median cingulate gyrus) was correlated with the improvement of symptoms, which was estimated by the Mongomery-Asberg Depression Scale (MADRS). FC has the potential to be an imaging biomarker that can predict the ketamine effect in MDD patients according to the receiver operating characteristic curve analysis.ConclusionOur results revealed that FC between the SMG and SMA and mACC was highly correlated with depressive symptoms and has the potential to be a neuroimaging biomarker to predict the effect of ketamine in MDD.

Time of day influences stress hormone response to ketamine.

Over 50% of depressed patients show hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Conventional therapy takes weeks to months to improve symptoms. Ketamine has rapid onset antidepressant effects. Yet its action on HPA axis activity is poorly understood. Here, we measured the corticosterone (CORT) response to ketamine administered at different times of day in the Wistar-Kyoto (WKY) rat. In male rats, blood was collected every 10min for 28 h using an automated blood sampling system. Ketamine (5/10/25 mg · kg) was infused through a subcutaneous cannula at two time points-during the active and inactive period. CORT levels in blood were measured in response to ketamine using a radioimmunoassay. WKY rats displayed robust circadian secretion of corticosterone and was not overly different to Sprague Dawley rats. Ketamine (all doses) significantly increased CORT response at both infusion times. However, a dose dependent effect and marked increase over baseline was observed when ketamine was administered during the inactive phase. Ketamine has a robust and rapid effect on HPA axis function. The timing of ketamine injection may prove crucial for glucocorticoid-mediated action in depression.

Ketamine promotes breast tumor growth in a mouse breast tumor model involving with high expression of miR-27b-3p and EGFR.

Non-medical use of ketamine as an adulterant to ecstasy is more prevalent than amphetamine in Taiwan. Ketamine's effect on immunosuppression might play some functional role in tumor growth, while it is still controversial whether ketamine abuse could increase tumor growth or not. This study aimed to investigate the influence of ketamine addiction in breast tumors and related gene expressions. The effect of ketamine treatment on proliferation, colony formation, migration, and invasion of triple-negative breast cancer cell line EO771 was examined. In addition, a ketamine addiction mice model was established by intraperitoneal injection (IP) of ketamine in mice and used to investigate the effects of ketamine addiction on tumor growth and the possible mechanisms. In the in vitro studies, ketamine treatment at different concentrations did not affect EO771 cell proliferation and colony formation. But ketamine did enhance migration and invasion of EO771 cells. The in vivo experiments showed significantly increased breast tumor volume and weight in ketamine-addicted mice than in normal saline groups. miR-27b-3p level, human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) significantly increased in tumors of ketamine addiction mice compared to control mice. In vivo evidence showed that Ketamine might increase tumor growth on the tumor microenvironment, and miR-27b-3p, HER2, and EGFR might play a role in the process.

N-Ethylnorketamine has anesthetic and analgesic effects with abuse liability

Arylcyclohexylamines is an ever-growing class of new psychoactive substances, including an increasing number of ketamine analogs. N-Ethylnorketamine (NENK) is a new synthetic ketamine analog that has emerged as an abused drug, but little is known about the pharmacological profile of NENK. In this study, we investigated the anesthetic and analgesic activity, abuse liability of NENK compared with ketamine. The ED50 values of anesthetic activity for NENK and ketamine were 96.9, 69.4 mg/kg, respectively. The ED50 values of analgesic activity for NENK and ketamine were 45.9 and 23.6 mg/kg, respectively. NENK induced significant conditioned place preference at a minimum dose of 10.0 mg/kg in mice, an effect comparable to that of ketamine (3.0 mg/kg). Acute injections of NENK or ketamine at 30.0 mg/kg enhanced locomotor activity, and repeated treatments with this dose induced locomotor sensitization after withdrawal. Taken together, these results clearly demonstrated that NENK has lower anesthetic and analgesic activity compared to ketamine, but has significant abuse liability.

Medial Septum Modulates Consciousness and Psychosis-Related Behaviors Through Hippocampal Gamma Activity.

Abnormally high-amplitude hippocampal gamma activity (30–100 Hz) in behaving animals is seen after a hippocampal seizure, following injection of phencyclidine (PCP) or ketamine, and transiently in a delirium stage during induction of general anesthesia. High-amplitude hippocampal gamma activity in behaving rats is associated with hyperactive behavior and impairment in sensorimotor gating and sensory gating. The medial septum is necessary for the high-amplitude gamma activity and abnormal behaviors observed following a hippocampal seizure or injection of PCP/ketamine. Glutamatergic projection of the hippocampus to the nucleus accumbens (NAC) and dopaminergic transmission in NAC is necessary for abnormal behaviors. Large hippocampal gamma waves are suggested to contribute to seizure-induced automatism following temporal lobe seizures, and the schizophrenia-like symptoms induced by PCP/ketamine. Low-amplitude gamma activity is found during general anesthesia, associated with loss of consciousness in humans and loss of righting reflex in animals. Local inactivation or lesion of the medial septum, NAC, and brain areas connected to the septohippocampal-NAC system attenuates the increase in hippocampal gamma and associated behavioral disruptions induced by hippocampal seizure or PCP/ketamine. Inactivation or lesion of the septohippocampal-NAC system decreases the dose of anesthetic necessary for gamma decrease and loss of consciousness in animals. Thus, it is proposed that the septohippocampal-NAC system serves to control consciousness and the behavioral hyperactivity and neural dysfunctions during psychosis.

The effect of ketamine on delta-range coupling between prefrontal cortex and hippocampus supported by respiratory rhythmic input from the olfactory bulb

Respiratory rhythm plays an important role in cognitive functions in rodents, as well as in humans. Respiratory related oscillation (RRO), generated in the olfactory bulb (OB), is an extrinsic rhythm imposed on brain networks. In rats, RRO can couple with intrinsic brain oscillations at theta frequency during sniffing and in the delta range outside of such episodes. Disruption of gamma synchronization in cortical networks by ketamine is well established whereas its effects on slow rhythms are poorly understood. We found in this study, that RRO in prefrontal cortex (PFC) and hippocampus (HC) remains present after ketamine injection, even on the background of highly unstable respiratory rate, co-incident with “psychotic-like” behavior and abnormal cortical gamma activity. Guided by the timing of ketamine-induced gamma reaction, pairwise coherences between structures exhibiting RRO and their correlation structure was statistically tested in 5-min segments post-injection (0–25 min) and during recovery (1, 5, 10 h). As in control, RRO in the OB was firmly followed by cortical-bound OB exits directed toward PFC but not to HC. RRO between these structures, however, significantly correlated with OB-HC but not with OB-PFC. The only exception to this general observation was observed during a short transitional period, immediately after injection. Ketamine has a remarkable history in psychiatric research. Modeling chronic NMDA-hypofunction using acute NMDA-receptor blockade shifted the primary focus of schizophrenia research to dysfunctional cortical microcircuitry and the recent discovery of ketamine’s antidepressant actions extended investigations to neurophysiology of anxiety and depression. Cortical oscillations are relevant for understanding their pathomechanism.