High-voltage electroencephalogram spindles in rats, aging and 5-HT2 antagonism.

We examined the effects of serotonin-2 (5-hydroxytryptamine-2, 5-HT2) receptor antagonists on the so-called high-voltage spindles (HVS, electroencephalographic patterns, characterized by large amplitude rhythmic waves mainly in the alpha band), recorded from the frontal cortex of young, middle-aged and old freely-moving rats during waking immobility. The study was based on the assumption that the effects of 5-HT2 receptor antagonists on the HVS activity depend on the age of rats, because there is evidence for an age-related decrease in the 5-HT2 binding sites density. Four parameters of the electroencephalogram (EEG) were used to characterize the HVS activity: the square root-transformed EEG peak power in the alpha band, the frequency corresponding to this peak (both measured from the EEG power spectra using the fast Fourier transform), the HVS mean duration, and the HVS incidence (both measured from the EEG records). The EEG parameters were analyzed after i.p. administration of three 5-HT2 receptor antagonists: ketanserin, ritanserin and cyproheptadine. In young rats, the three drugs increased the alpha power, but did not change the alpha peak-corresponding frequency. Ketanserin and ritanserin did not change the HVS mean duration and HVS incidence, while cyproheptadine increased both these parameters in young rats. In middle-aged and old untreated rats, the HVS activity was significantly increased. The three 5-HT2 antagonists did not change the HVS activity in aged rats, which could be due to age-related suppression of the 5-HT2 receptor functions.

Age-dependent effect of ketanserin on the sleep-waking phases in rats.

The age-dependent effect of the specific 5-HT2 receptor antagonist ketanserin at two doses (1 mg/kg and 6 mg/kg) on six sleep-waking phases was electroencephalographically (EEG) examined in young, middle-aged, and old male Wistar rats. Because 5-HT2 receptor binding sites decrease with aging, the question of whether ketanserin can produce any effect on sleep-wake in advanced age was addressed. Ketanserin enhanced deep slow wave sleep in the three age groups. However, in the old rats this effect was much less pronounced and did not depend on the dose. Only in the young and middle-aged animals, ketanserin reduced wakefulness in a dose-dependent manner. The suppression of paradoxical sleep with ketanserin did not depend on the age. The results suggest that the model of aging may be useful to study the functional role of 5-HT2 receptors in sleep-waking regulation.

Age-related effect of ritanserin on the sleep-waking phases in rats.

The age-related effect of the specific 5-hydroxytryptamine-2A/2C (5-HT(2A/2C)) antagonist ritanserin at two doses 0.63 mg/kg and 2.5 mg/kg) on six sleep-waking phases in young, middle-aged, and old male Wistar rats was electroencephalographically (EEG) examined. Only in the young and middle-aged rats, ritanserin enhanced slow wave sleep and reduced wakefulness in a dose-dependent manner. Ritanserin suppressed paradoxical sleep, such that this effect did not depend on the age. Although the effect of ritanserin on slow wave sleep was significantly smaller in the old compared to the young and the middle-aged rats, ritanserin produced an apparent sleep-improving effect in the old age group.

Quantitative electroencephalographic changes due to middle cerebral artery occlusion by endothelin 1 in conscious rats.

The powerful vasoconstrictor peptide endothelin-1 (ET1) has been shown to reduce local cerebral blood flow in brain areas supplied by the middle cerebral artery (MCA) to a pathologically low level upon intracerebral injection adjacent to the MCA. This reduction manifests itself as an ischemic infarct, that is fully developed within 3 days after ET1 injection. The aim of the present study is to examine the effect of ET1 on electroencephalographic (EEG) activity. ET1 was microinjected unilaterally at a dose of 60 pmol in 3 microl of saline to the MCA in conscious rats. EEG signals were recorded from the frontoparietal cortical area, supplied by MCA, from the first up to the fourteenth day after ET1 injection. EEG activity was analyzed by the fast Fourier transformation. A significant shift to a lower EEG frequency, i.e., augmentation of slow waves and a reduction of alpha-like and faster EEG waves was found post-ET1. This effect was maximal after 3-7 days when the most severe destruction of neurons in this cortical area occurs, as has been previously demonstrated. The results suggest that the quantitative EEG analysis may provide useful additional information about the functional disturbances associated with focal cerebral ischemia.

Power spectral electroencephalogram analysis of the effects of ritanserin in freely moving rats during quiet waking.

Changes in the spectral characteristics of the Fast Fourier Transformed (FFT) electroencephalogram (EEG) recorded from the frontal cortex of freely moving rats during quiet waking were studied after blockade of the 5-hydroxytryptamine-2 (5-HT2) receptors by the potent and long acting 5-HT2 antagonist ritanserin administered intraperitoneally (i.p.) at two doses (0.63 and 2.5 mg/kg). The rationale of this approach was to evaluate the subtle ritanserin-induced changes in the EEG in the frequency domain, and thus obtain more information about the neurophysiological effects mediated by brain 5-HT2 receptors and about the mechanisms underlying ritanserin's ability to increase sleep at the expense of wakefulness. Ritanserin induced significant changes in the power spectrum of EEG recorded from the frontal cortex. The activation index (the ratio of the dominant frequency in the power spectrum to the total power) significantly decreased after ritanserin, which was due to the increased EEG power in all frequency bands (except for beta 2) and to the decreased dominant frequency in the EEG spectrum, suggesting ritanserin-reduced EEG activation during quiet waking. The results favor the view of the excitatory modulating action of serotonin mediated via cortical 5-HT2 receptors and suggest that ritanserin could cause a faster transition from waking to sleep.

Ritanserin-induced changes in sleep-waking phases in rats.

Ten male Wistar rats were chronically implanted with conventional electrodes for sleep-waking stages detection. Three 12-hour electroencephalographic (EEG) registrations were performed once a week, after i.p. injection of the serotonin-2 (5-HT2) antagonist ritanserin at two doses (0.63 mg/kg and 2.5 mg/kg) and after ritanserin vehicle. The goal of the present study was to examine the effects of ritanserin on sleep-waking phases, and to obtain additional data about the participation of 5-HT2 receptors in the regulation of sleep and wake behaviour. Six sleep-waking stages were detected: active waking, quiet waking, light slow-wave sleep, deep slow-wave sleep, intermediate stage of sleep and paradoxical sleep. Each of the 12-h postdrug EEG records was divided into 3 consecutive 4-hour periods and the sleep-waking stages were scored visually for every minute of the whole postdrug period. The three periods were compared in order to evaluate the effect of ritanserin in dynamics. The results obtained showed a significant decrease in wakefulness and paradoxical sleep, a significant increase in slow-wave sleep (mainly the deep slow-wave sleep) and in the intermediate stage of sleep. These changes in the sleep-waking phases occurred in a dose-dependent manner, the larger the dose of ritanserin, the stronger the effect of ritanserin. The changes were more pronounced during the first 4-h period and then a restoration in the sleep-waking phases took place except for the paradoxical sleep.