It has been proposed that the schizophrenic symptoms may be emerged from the dysfunctional connection and abnormal glutamate neurotransmission between prefrontal and temporolimbic cortex. Thus, we examined the functional connectivity between entorhinal cortex-hippocampus in the schizophrenic animal model induced by the NMDA receptor channel blocker, ketamine. Under ketamine+xylazine anesthesia, the electrodes for recording and stimulating were implanted into the hippocampus of the male rat. Recording of EEG and EP was started 3 or more days after operation in 3 different behavioral states (normal mobile and immobile, and ketamine-injected). Each hippocampal area had a characteristic EP. While it did not produce changes on the normal EPs, ketamine produced greater changes on the normal EEG : prominant theta in normal mobile state ; fast and irregular wave accompanying with 1-2 Hz spikes in normal immobile states and ; fAst and irregular rhythm with spindles of 2.5 Hz and 30 Hz which were prominant on DG and CA3 in ketamine-injected state. Log scale of spectrum showed that ketamine increased the power of 6-8 Hz band on CA1 radiatum and of the band over 25 Hz on DG. Also ketamine disrupted the correlated electrical activity among several hippocampal areas. These results may suggest that the symptom of schizophrenics is emerged from reduction of correlated activity but increase of irregular activity over the cortical area and uncontrolled input which is mediated by NMDA receptor.
Anesthesia ; Animals ; Electrodes ; Electroencephalography ; Glutamic Acid ; Hippocampus* ; Humans ; Ketamine ; Male ; Models, Animal* ; N-Methylaspartate ; Rats* ; Schizophrenia ; Synaptic Transmission

OBJECTIVE : Modafinil, methylphenidate, and caffeine are wakefulness-promoting substances. Previously, it was reported that caffeine-induced wakefulness differs from natural wakefulness in terms of the EEG spectral profiles. In order to evaluate whether wakefulness induced by other psychostimulants differs from both caffeine-induced and natural wakefulness, we examined the effects of the psychostimulants on sleep-wake architecture and EEG spectral profiles. METHODS : Eighteen Sprague-Dawley male rats underwent an EEG/EMG recording session from 10 : 30 to 17 : 30. They received caffeine (7.5, 15, 30 mg/kg i.p.), methylphenidate (1, 2, 5, 10 mg/kg i.p.) or modafinil (5, 10, 25, 50, 100 mg/kg i.p.) at 13 : 30. The number, total duration, and average duration of sleepwake states were obtained. EEG band powers were calculated by spectral analysis. Frequency bands were divided into the following ranges : D1, 1-2.5 Hz ; D2, 2.5-4.5 Hz ; T1, 4.5-7 Hz ; T2, 7-10 Hz ; SI, 10-14 Hz ; B1, 14-22 Hz ; B2, 22-34 Hz ; GA, 34-50 Hz. RESULTS : All three psychostimulants significantly and dose-dependently increased active wake duration and decreased slow-wave sleep. Equipotent doses of caffeine, methylphenidate, and modafinil for increasing active wake and decreasing slow-wave sleep were 7.5 mg/kg, 10 mg/kg, and 100 mg/kg, respectively. In equipotent doses, an increase of active wake duration by caffeine and methylphenidate was attributed to increases of both frequency and average duration of active wake state, whereas increase of active wake duration by modafinil was attributed to increase of average duration of active wake state only. In equipotent doses, caffeine and methylphenidate decreased the power of lower frequency bands (1-22 Hz), whereas modafinil did not. During slow-wave sleep, modafinil and methylphenidate increased the power of lower frequency bands, but caffeine did not. All the psychostimulants increased the power of the GA band, which was more prominent in the frontal cortex than the parietal cortex. CONCLUSION : These results suggest that moda-nil-induced wakefulness differs from caffeine- or methylphenidate-induced wakefulness in terms of EEG spectral profiles and sleep-wake architecture.
Animals ; Benzhydryl Compounds ; Caffeine ; Electroencephalography ; Humans ; Male ; Methylphenidate ; Rats ; Wakefulness

Although quantitative EEG parameters, such as spectral band powers, are sensitive to centrally acting drugs in dose- and time-related manners, changes of the EEG parameters are redundant. It is desirable to reduce multiple EEG parameters to a few components that can be manageable in a real space as well as be considered as parameters representing drug effects. We calculated factor loadings from normalized values of eight relative band powers (powers of 0.5, 1.0~2.0, 2.5~4.0, 4.5~5.5, 6.0~8.0, 8.5~12.0, 12.5~24.5, and 25~49.5 Hz bands expressed as ratios of the power of 0.5-49.5 Hz band) of EEG during pre-drug periods (11:00~12:00) by factor analysis and constructed a two-dimensional canonical space (reference canonical space) by canonical correlation analysis. Eight relative band powers of EEG produced by either physostigmine or yohimbine were reduced to two canonical scores in the reference canonical space. While changes of the band powers produced by physostigmine and yohimbine were too redundant to describe the difference between two drugs, locations of two drugs in the reference canonical space represented the difference between two drug's effects on EEG. Because the distance between two locations in the canonical space (Mahalanobis distance) indicates the magnitude of difference between two different sets of EEG parameters statistically, the canonical scores and the distance may be used to quantitatively and qualitatively describe the dose-dependent and time-dependent effects and also tell similarity and dissimilarity among effects. Then, the combination of power spectral analysis and statistical analysis may help to classify actions of centrally acting drugs.
Animals ; Electroencephalography ; Factor Analysis, Statistical ; Physostigmine ; Rats ; Yohimbine

The dose-related effects of halothane, enflurane, and isoflurane on the rat EEG were evaluated qusntitstively by spectral analysis of the EEG recorded from the rat skull. The anesthetics were inhaled by animal ventilator into 10L glass bottle, in which the preparated rats were placed, at various concentrations, and then bipolar EEG was recorded from the rat skull and its spectrum was calculated by power speetral analysis. The density of each spectral bands (delta 1-3.25, theta 3.5-7.75, alpha 8-12.25, and beta 13-31.75Hz), total density, delta ratio, spectral edge frequency, and medisn power frequency were derived from the spectra. With inspection of conventional EEG, 1.5 MAC of hslothane revealed spindles, but higher dose decreased the amplitude. 1.5 MAC of enflurane revealed a lot of spike waves but 2.0 MAC revealed several spike waves and decreased the amplitude, and 1.5 MAC isoflurane revealed isolated spike waves but 2.0 MAC revealed cerebro- electrical silence. In quantitative spectral analysis of EEG, significant EEG changes were identified during inhalation of all anestheties. In halothane dominent frequencies in EEG were delta waves at 1.5 MAC and 2.0 MAC. In enflurane dominent waves in EEG were theta waves at 1.5 MAC and 2.0 MAC and in isoflurane those were theta waves. Taken together, these findings suggest that analysis for EEG parameters derived from power spectral analysis could be applied to determine the depth of halothane, enflurane, and isoflurane anesthesia.
Anesthesia ; Anesthetics ; Animals ; Electroencephalography* ; Enflurane* ; Glass ; Halothane* ; Inhalation* ; Isoflurane* ; Rats* ; Skull ; Spectrum Analysis ; Ventilators, Mechanical

The effects of an antipsychotic, chlorpromazine, on the electroencephalogram (EEG) were observed while rats were awake but immobile. The time course and the dose-dependency of the EEG changes were examined. The method of the power spectrum analysis was used to examine the EEG changes by the drug. The bands were divided into delta (1 ~ 3.5 Hz), theta (3.5 ~ 8 Hz), alpha (8 ~ 13 Hz), beta1 (13 ~ 21 Hz), beta2 (21 ~ 30 Hz) and gamma (30 ~ 50 Hz). In rats, the low dose of chlropromazine (1 mg/kg, i.p.) produced a significant increase in the power of the beta1 band. The higher doses (5, 10 mg/kg, i.p.) produced a significant increase in the power of the delta, theta, alpha and beta1 bands, and the decrease in the power of the gamma band. The powers of the bands changed dose-dependently. Then, the authors discussed whether the EEG effects produced by a drug are associated with the accompanying behavioral changes specifically.
Animals ; Chlorpromazine* ; Electroencephalography ; Rats* ; Spectrum Analysis

The sleep homeostatic response significantly affects the state of anesthesia. In addition, sleep recovery may occur during anesthesia, either via a natural sleep-like process to occur or via a direct restorative effect. Little is known about the effects of isoflurane anesthesia on sleep homeostasis. We investigated whether 1) isoflurane anesthesia could provide a sleep-like process, and 2) the depth of anesthesia could differently affect the post-anesthesia sleep response. Nine rats were treated for 2 hours with ad libitum sleep (Control), sleep deprivation (SD), and isoflurane anesthesia with delta-wave-predominant state (ISO-1) or burst suppression pattern-predominant state (ISO-2) with at least a 1-week interval. Electroencephalogram and electromyogram were recorded and sleep-wake architecture was evaluated for 4 hours after each treatment. In the post-treatment period, the duration of transition to slow-wave-sleep decreased but slow wave sleep (SWS) increased in the SD group, but no sleep stages were significantly changed in ISO-1 and ISO-2 groups compared to Control. Different levels of anesthesia did not significantly affect the post-anesthesia sleep responses, but the deep level of anesthesia significantly delayed the latency to sleep compared to Control. The present results indicate that a natural sleep-like process likely occurs during isoflurane anesthesia and that the post-anesthesia sleep response occurs irrespective to the level of anesthesia.
Anesthesia ; Animals ; Electroencephalography ; Homeostasis ; Isoflurane ; Rats ; Sleep Deprivation ; Sleep Stages

Head restraining is an experimental technique that firmly secures the animal's head to a fixation apparatus for the precise control and sensing of behaviors. However, procedural and surgical difficulties and limitations have been obstructing the use of the technique in neurophysiological and behavioral experiments. Here, we propose a novel design of the head-restraining apparatus which is easy to develop and convenient for practical use. Head restraining procedure can be completed by sliding the head mounter, which is molded by dental cement during implantation surgery, into the port, which serves as matching guide rails for the mounter, of the fixation bar. So neither skull-attached plates nor screws for fixation are needed. We performed intracranial self stimulation experiment in rats using the newly designed device. Rats were habituated to acclimatize the head-restraint environment and trained to discriminate two spatially distinguished cues using a customized push-pull lever as an operandum. Direct electrical stimulation into the medial forebrain bundle served as reward. We confirmed that head restraining was stable throughout experiments and rats were able to learn to manipulate the lever after successful habituation. Our experimental framework might help precise control or sensing of behavior under head fixed rats using direct electrical brain stimulation as a reward.
Animals ; Brain ; Conditioning, Operant ; Cues ; Dental Cements ; Electric Stimulation ; Fungi ; Head* ; Medial Forebrain Bundle ; Rats* ; Reward ; Self Stimulation*

The effects of different doses of tramadol on analgesia and electroencephalographic (EEG) spectral parameters were compared in rats. Saline or tramadol 5, 10, 20 or 40 mg/kg was administered. The degree of analgesia was evaluated by tail-flick latency, and the degree of seizure was measured using numerical seizure score (NSS). Additionally, band powers, median power frequency and spectral edge frequency 95 were measured to quantify the EEG response. All doses of tramadol produced spike-wave discharge. Tramadol significantly and dose-dependently increased the analgesia, but these effects did not correspond with the changes in the EEG spectral parameters. NSS significantly increased in the Tramadol 20 and 40 mg/kg treatment groups compared to the Control and TRA5 groups, and two rats given 40 mg/kg had convulsions. In conclusion, tramadol dose-dependently increased the analgesic effect, and the 10 mg/kg dose appears to be a reliable clinical dose for analgesia in rats, but dose-dependent increases in analgesia and seizure severity did not correlate with EEG spectral parameters.
Analgesia ; Animals ; Electroencephalography ; Rats ; Seizures ; Tramadol

This study was designed to evaluate the efficacy of dynamic parameters, such as correlation dimension D2, by comparing spectral electroencephalographic (EEG) parameters. These parameters are used to estimate the depth of halothane anesthesia as defined by the presence of body movement in response to a tail clamp. Six rats were used and each of them was exposed to halothane sequentially at the concentrations of 0%, 0.5%, 1.0% and 1.5% for 30 min. A tail clamp was applied every five min and the movements were recorded at each concentration level. The spectral parameters and the dynamic parameters were derived from 20-sec and 10-sec segments, respectively, from the last 5-mins of EEG recording at each concentration level. Correlation coefficients between the parameters and the movements were calculated. Standardized values of three parameters, betaL power, median power frequency (MPF), and D2 were derived by calculation based on the number of animals showing the movement in response to a tail clamp. The betaL power had the largest correlation coefficient to spontaneous movement and to the response to a tail clamp than any other band parameter. MPF had a better correlation with the movement than 90% spectral edge frequency. Among the dynamic parameters, D2 on the parietal cortex had a better correlation with the movement. The level of deviation and variation of standardized D2, MPF, and betaL were significant (p < 0.01). The order of deviation and variation was; betaL power > MPF > D2. The correlation dimension serves as a better index for the depth of halothane anesthesia defined in forms of a response to external stimulation.
Anesthesia ; Animals ; Electroencephalography ; Halothane* ; Rabeprazole ; Rats

Migraine is a neurological disorder characterized by recurrent and disabling severe headaches. Although several anticonvulsant drugs that block voltage-dependent Na⁺ channels are widely used for migraine, far less is known about the therapeutic actions of carbamazepine on migraine. In the present study, therefore, we characterized the effects of carbamazepine on tetrodotoxin-resistant (TTX-R) Na⁺ channels in acutely isolated rat dural afferent neurons, which were identified by the fluorescent dye DiI. The TTX-R Na⁺ currents were measured in medium-sized DiIpositive neurons using the whole-cell patch clamp technique in the voltage-clamp mode. While carbamazepine had little effect on the peak amplitude of transient Na⁺ currents, it strongly inhibited steady-state currents of transient as well as persistent Na⁺ currents in a concentration-dependent manner. Carbamazepine had only minor effects on the voltage-activation relationship, the voltage-inactivation relationship, and the use-dependent inhibition of TTX-R Na⁺ channels. However, carbamazepine changed the inactivation kinetics of TTX-R Na⁺ channels, significantly accelerating the development of inactivation and delaying the recovery from inactivation. In the current-clamp mode, carbamazepine decreased the number of action potentials without changing the action potential threshold. Given that the sensitization of dural afferent neurons by inflammatory mediators triggers acute migraine headaches and that inflammatory mediators potentiate TTX-R Na⁺ currents, the present results suggest that carbamazepine may be useful for the treatment of migraine headaches.
Action Potentials ; Animals ; Anticonvulsants ; Carbamazepine* ; Headache ; Kinetics ; Migraine Disorders ; Nervous System Diseases ; Neurons* ; Neurons, Afferent ; Rats ; Sodium Channels ; Trigeminal Ganglion*