***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: BACKGROUND Currently , no pharmacological treatments for bipolar depression exist that exert rapid ( within hours ) antidepressant or antisuicidal effects . We previously reported that intravenous administration of the N-methyl-D-aspartate antagonist ketamine produced rapid antidepressant effects in patients with treatment-resistant bipolar depression . The present study sought to replicate this finding in an independent sample . METHODS In this double-blind , r and omized , crossover , placebo-controlled study , 15 subjects with DSM-IV bipolar I or II depression maintained on therapeutic levels of lithium or valproate  received a single intravenous infusion of either ketamine hydrochloride ( .5 mg/kg ) or placebo on 2 test days 2 weeks apart . The primary outcome measure was the Montgomery-Asberg Depression Rating Scale , which was used to rate overall depressive symptoms at baseline ; at 40 , 80 , 110 , and 230 minutes postinfusion ; and on days 1 , 2 , 3 , 7 , 10 , and 14 postinfusion . RESULTS Within 40 minutes , depressive symptoms , as well as suicidal ideation , significantly improved in subjects receiving ketamine compared with placebo ( d = .89 , 95 % confidence interval = .61 - 1.16 , and .98 , 95 % confidence interval = .64 - 1.33 , respectively ) ; this improvement remained significant through day 3 . Seventy-nine percent of subjects responded to ketamine and 0 % responded to placebo at some point during the trial . The most common side effect was dissociative symptoms , which occurred only at the 40-minute time point . CONCLUSIONS This study replicated our previous finding that patients with bipolar depression who received a single ketamine infusion experienced a rapid and robust antidepressant response . In addition , we found that ketamine rapidly improved suicidal ideation in these patients Several electrical neural oscillatory abnormalities have been associated with schizophrenia , although the underlying mechanisms of these oscillatory problems are unclear . Animal studies suggest that one of the key mechanisms of neural oscillations is through glutamatergic regulation ; therefore , neural oscillations may provide a valuable animal– clinical interface on study ing glutamatergic dysfunction in schizophrenia . To identify glutamatergic control of neural oscillation relevant to human subjects , we studied the effects of ketamine , an N-methyl-D-aspartate antagonist that can mimic some clinical aspects of schizophrenia , on auditory-evoked neural oscillations using a paired-click paradigm . This was a double-blind , placebo-controlled , crossover study of  ketamine vs saline infusion on 10 healthy subjects . Clinical ly , infusion of ketamine in subanesthetic dose significantly increased thought disorder , withdrawal – retardation , and dissociative symptoms .  Ketamine significantly augmented high-frequency oscillations ( gamma b and at 40–85 Hz , p=0.006 ) and reduced low-frequency oscillations ( delta b and at 1–5 Hz , p<0.001 ) compared with placebo . Importantly , the combined effect of increased gamma and reduced delta frequency oscillations was significantly associated with more withdrawal – retardation symptoms experienced during ketamine administration ( p=0.02 ) . Ketamine also reduced gating of the theta-alpha ( 5–12 Hz ) range oscillation , an effect that mimics previously described deficits in schizophrenia patients and their first-degree relatives . In conclusion , acute ketamine appeared to mimic some aspects of neural oscillatory deficits in schizophrenia , and showed an opposite effect on scalp-recorded gamma vs low-frequency oscillations . These electrical oscillatory indexes of subanesthetic ketamine can be potentially used to cross-examine glutamatergic pharmacological effects in translational animal and human studies We administered ketamine to schizophrenic individuals in a double-blind , placebo-controlled design using a range of subanesthetic doses ( 0.1 , 0.3 , and 0.5 mg/kg ) to evaluate the nature , dose characteristics , time course , and neuroleptic modulation of N-methyl-D-aspartate ( NMDA ) antagonist action on mental status in schizophrenia . Ketamine induced a dose-related , short ( < 30 minutes ) worsening in mental status in the haloperidol-treated condition , reflected by a significant increase in BPRS total score for the 0.3 mg/kg ( p = . 005 ) and 0.5 mg/kg ( p = . 01 ) challenges . Positive symptoms ( hallucinations , delusions , thought disorder ) , not negative symptoms accounted for these changes . These ketamine-induced psychotic symptoms were strikingly reminiscent of the subject 's symptoms during active episodes of their illness . Results from six patients who were retested in the same design after being neuroleptic-free for 4 weeks failed to indicate that haloperidol blocks ketamine-induced psychosis . Several subjects evidence d delayed or prolonged ( 8–24 hours ) psychotomimetic effects such as worsening of psychosis with visual hallucinations . These data suggest that antagonism of NMDA-sensitive glutamatergic transmission in brain exacerbates symptoms of schizophrenia OBJECTIVE To investigate the effects of ketamine on the electroencephalogram ( EEG ) of the horse . STUDY DESIGN Prospect i ve experimental study . ANIMALS Eight Welsh mountain pony geldings weighing between 280 and 330 kg , 5 to 9 years old . METHODS During halothane anesthesia at an end-tidal halothane concentration between 0.75 and 0.85 % , the EEG frequency power spectrum and the auditory evoked potential were recorded while an infusion of ketamine was given . Ketamine 200 mg was infused over 5 minutes in 8 ponies . The effects of ketamine on the EEG were recorded continuously during the infusion and for a further 55 minutes . RESULTS The ketamine infusion produced a plasma ketamine concentration that was significantly greater than the baseline until 7 minutes after the start of the infusion . The highest recorded ketamine concentration was 4.2+/-1.1 microg/ml recorded at 5 minutes after the start of the infusion . The spectral edge and median frequency of the EEG and the midlatency of the auditory evoked potential were compared with those recorded before the start of the infusion . The spectral edge , median frequencies and mid-latency of the auditory evoked potential were reduced by 21+/-13 % , 31+/-20 % and 19+/-36 % respectively ( mean + /- SD ) . Only the reduction in spectral edge frequency reached statistical significance . CONCLUSIONS These results compared with those from other anesthetic and sedative agents suggest that the spectral edge frequency is an indicator of general central nervous system depression whereas the median frequency may be an indicator of antinociception This r and omized , placebo-controlled , double-blind study was the first to evaluate the antidepressant efficacy , safety , and tolerability of an NR2B subunit-selective N-methyl-D-aspartate receptor antagonist , CP-101,606 .  Subjects had major depression , according to Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition criteria and a history of treatment refractoriness to least 1 adequate trial of a selective serotonin reuptake inhibitor . The study had 2 treatment periods . In period 1 , subjects first received a 6-week open-label trial of paroxetine and a single-blind , intravenous placebo infusion . Period 1 nonresponders ( n = 30 ) then received a r and omized double-blind single infusion of CP-101,606 or placebo plus continued treatment with paroxetine for up to an additional 4 weeks ( period 2 ) . Depression severity was assessed using the Montgomery-Åsberg Depression Rating Scale and 17-item Hamilton Depression Rating Scale . On the prespecified main outcome measure ( change from baseline in the Montgomery-Åsberg Depression Rating Scale total score at day 5 of period 2 ) , CP-101,606 produced a greater decrease than did placebo ( mean difference , 8.6 ; 80 % confidence interval , −12.3 to −4.5 ) ( P < 0.10 ) . Hamilton Depression Rating Scale response rate was 60 % for CP-101,606 versus 20 % for placebo . Seventy-eight percent of CP-101,606-treated responders maintained response status for at least 1 week after the infusion . CP-101,606 was safe , generally well tolerated , and capable of producing an antidepressant response without also producing a dissociative reaction . Antagonism of the NR2B subtype of the N-methyl-D-aspartate receptor may be a fruitful target for the development of a new antidepressant with more robust effects and a faster onset compared with those currently available and capable of working when existing antidepressants do not Background : The potential adverse effects of ketamine in neurosurgical anesthesia have been well established and involve increased intracranial pressure ( ICP ) and cerebral blood flow . However , reexamination of ketamine is warranted because data regarding the effects of ketamine on cerebral hemodynamics are conflicting . Methods : Eight patients with traumatic brain injury were studied . In all patients , ICP monitoring was instituted before the study . Control of ICP ( less than 25 mmHg ) , hemodynamic values , and blood gas tension ( partial pressure of carbon dioxide in arterial blood between 35–38 mmHg ) was obtained with propofol infusion ( 3 mg [ center dot ] kg sup ‐1 [ center dot ] h sup ‐1 ) and mechanical ventilation . The effects of three doses of ketamine , 1.5 , 3 , and 5 mg/ kg , respectively , on ICP , cerebral perfusion pressure , jugular vein bulb oxygen saturation , middle cerebral artery blood flow velocity , and electric activity of the brain ( EEG ) were measured . The three doses were administered intravenously at 6‐h intervals over 30 s through a central venous line . Systemic and cerebral hemodynamics and end‐tidal carbon dioxide were continuously monitored and recorded at 1‐min intervals throughout the 30‐min study periods . Results : Ketamine , in all three doses studied ( 1.5 , 3 , and 5 mg/kg ) was associated with a significant decrease in ICP ( mean + /‐ SD : 2 + /‐ 0.5 mmHg [ P < 0.05 ] , 4 + /‐ 1 mmHg [ P < 0.05 ] , and 5 + /‐ 2 mmHg [ P < 0.05 ] ) among the study patients regardless of the ketamine dose used . There were no significant differences in cerebral perfusion pressure , jugular vein bulb oxygen saturation , and middle cerebral artery blood flow velocity . Ketamine induced a low‐amplitude fast‐activity electroencephalogram , with marked depression , such as burst suppression . Conclusions : These results suggest that ketamine may not adversely alter cerebral hemodynamics of mechanically ventilated head‐trauma patients se date d with propofol . These encouraging results should be confirmed in larger groups of similar patients The electroencephalographic ( EEG ) effects of ketamine anaesthesia have been a subject of earlier studies in man ' and in a n i r n a l ~ . ~ ~ ~ The present investigation was part of a larger study into the cardiovascular and electroencephalographic changes following the injection of various anaesthetics including A l t h e ~ i n . ~ . ~ Equivalent doses of ketamine were given twice at different rates of administration in two groups of patients and cerebral electrical activity was assessed . This was done both by conventional EEG recording and a single channel monitoring device ( cerebral function monitor or CFM),6 the use of which has already been described both in relation to anae ~ thesia,~ cerebral anoxia ' and cardiovascular surgery . ' The aim of this study was to determine the time of onset and the sequence of changes in the cerebral activity due to ketamine BACKGROUND To characterize further behavioral , cognitive , neuroendocrine , and physiological effects of subanesthetic doses of ketamine hydrochloride in healthy human subjects .  Ketamine , a phencyclidine hydrochloride derivative , is a dissociative anesthetic and a noncompetitive antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptor . METHODS Nineteen healthy subjects recruited by advertisements from the community participated in this r and omized , double-blind , placebo-controlled study . Subjects completed three test days involving the 40-minute intravenous administration of placebo , ketamine hydrochloride ( 0.1 mg/kg ) , or ketamine hydrochloride ( 0.5 mg/kg ) . Behaviors associated with the positive and negative symptoms of schizophrenia were assessed by using the Brief Psychiatric Rating Scale . Changes in perception and behaviors associated with dissociative states were assessed by the Perceptual Aberration Subscale of the Wisconsin Psychosis Proneness Scale and the Clinician-Administered Dissociative States Scale . Cognitive function was assessed by using the ( 1 ) Mini-Mental State Examination ; ( 2 ) tests sensitive to frontal cortical dysfunction , including 
    Output:
    
We also discuss some of the current hypotheses that are considered to account for the actions of  NMDAR antagonists on these frequency b and s. The data emphasize a close relationship between altered oscillatory activity and NMDAR blockade , with both local and large-scale networks accounting for their effects .
These findings may have fundamental implication s for the psychotomimetic effects produced by NMDAR antagonists