Effects of Single Treatment of Anti-Dementia Drugs on Sleep-Wake Patterns in Rats

We studied the effects of acetylcholinesterase inhibitors, donepezil and galantamine, and an N-methyl-D-aspartate (NMDA) receptor blocker, memantine, on sleep-wake architecture in rats. Screw electrodes were chronically implanted into the frontal and parietal cortex for the electroencephalography (EEG). EEG was recorded with a bio-potential amplifier for 8 h from 09:30 to 17:30. Vibration was recorded to monitor animal activity with a vibration measuring device. Sleep-wake states such as wake (W), slow-wave sleep (S) and paradoxical or rapid eye movement sleep (P), were scored every 10 sec by an experimenter. We measured mean episode duration and number of episode to determine which factor sleep disturbance was attributed to. Donepezil and memantine showed a significant increase in total W duration and decreases in total S and P duration and delta activity. Memantine showed increases in sleep latency and motor activity. Changes of S and P duration in memantine were attributed from changes of mean episode duration. Galantamine had little effect on sleep architecture. From these results, it is showed that galantamine may be an anti-dementia drug that does not cause sleep disturbances and memantine may be a drug that causes severe sleep disturbance.

Effects of Isoflurane Anesthesia on Post-Anesthetic Sleep-Wake Architectures in Rats

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.

The Effects of Tramadol on Electroencephalographic Spectral Parameters and Analgesia in Rats

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.

Role of Dopamine Receptors on Electroencephalographic Changes Produced by Repetitive Apomorphine Treatments in Rats

Repeated psychostimulants induce electroencephalographic (EEG) changes, which reflect adaptation of the neural substrate related to dopaminergic pathways. To study the role of dopamine receptors in EEG changes, we examined the effect of apomorphine, the dopamine D1 receptor antagonist, SCH-23390, and the D2 receptor antagonist, haloperidol, on EEG in rats. For single and repeated apomorphine treatment groups, the rats received saline or apomorphine for 4 days followed by a 3-day withdrawal period and then apomorphine (2.5 mg/kg, i.p.) challenge after pretreatment with saline, SCH-23390, or haloperidol on the day of the experiment. EEGs from the frontal and parietal cortices were recorded. On the frontal cortex, apomorphine decreased the power of all the frequency bands in the single treatment group, and increased the theta (4.5~8 Hz) and alpha (8~13 Hz) powers in the repeated treatment group. Changes in both groups were reversed to the control values by SCH-23390. On the parietal cortex, single apomorphine treatment decreased the power of some frequency bands, which were reversed by haloperidol but not by SCH-23390. Repeated apomorphine treatment did not produce significant changes in the power profile. These results show that adaptation of dopamine pathways by repeated apomorphine treatment could be identified with EEG changes such as increases in theta and alpha power of the frontal cortex, and this adaptation may occur through changes in the D1 receptor and/or the D2 receptor.

Effect of Modafinil and Methylphenidate on Sleep-Wake Architecture and EEG Power Spectra in Rats / 대한정신약물학회지

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.

Effect of Injectable Chitosan Bead Encapsulating Calcium Sulfate on Bony Consolidation in Distraction Osteogenesis

The purpose of this project was to study the effect of injectable chitosan bead encapsulating calcium sulfate, which makes sustained release of chitosan and calcium sulfate after implantation, on early bony consolidation in distraction osteogenesis of a dog model. Forty five dogs were used for this study. An external distraction device was applied to the mandibular body after vertical osteotomy and the mandibular distraction was started five days after the operation at a rate of 1mm per day up to a 10mm distraction. The experimental group was divided into a control group(I), hyaluronic acid group(II), chitosan group(III), calcium sulfate group(IV), and injectable chitosan bead encapsulating calcium sulfate group(V). Normal saline was injected in the group I. In the group II, a 1-ml volume of hyaluronic acid solution was injected into the distracted area. In the group III, a 1-ml of injectable solution of chitosan mixed with hyaluronic acid was implanted. In the group IV, a 1-ml of injectable solution of calcium sulfate mixed with hyaluronic acid was implanted. In the group V, injectable form of powders of chitosan bead encapsulating calcium sulfate mixed with a 1-ml volume of hyaluronic acid was implanted. Bone mineral density was measured in each group at third and sixth week. The mean three point failure load was measured in each group. In histological findings, new bone was generated in all groups. In the group IV and V, the formation of active woven bone was observed throughout the distracted area at sixth week. The amount of new bone formation in the distracted zone was in the order of the group IV and V, group III and group II, and control group. In conclusion, these findings suggest that injectable chitosan bead encapsulating calcium sulfate appears to be effective in early bony consolidation in distraction osteogenesis.

Effect of Growth Hormone on Early Bony Regeneration in Distraction Osteogenesis

The purpose of this project was to study the effect of growth hormone on early bony consolidation in distraction osteogenesis of a dog mandible. Sixteen dogs were used for this study. An external distraction device was applied to the mandibular body and the mandibular distraction was started five days after the operation at a rate of 1 mm per day up to a 10-mm distraction. Dogs in the growth hormone group received a daily subcutaneous injection of 1 IU of recombinant human growth hormone per kilogram of body weight per week. Normal saline was injected in the control group. Bone mineral density was higher in the growth hormone group than the control group in the whole period. Bone mechanical strength was 300% higher in the growth hormone group than that in the control group. However, results were more suggestive than conclusive. Upon histological examination, the formation of a substantial amount of active woven bone was observed throughout the distracted zone in 6 weeks in the growth hormone group. In the control group, new bone was generated from the edge to the center of the distracted zone. But, the most central area of the distracted zone was filled with fibrous tissue in 6 weeks. In conclusion, growth hormone appears to be effective in early bony consolidation in distraction osteogenesis.