Brain histamine levels and neocortical slow-wave activity in rats with portacaval anastomosis

To determine whether the increased histamine levels in the brain of rats wi th portacaval anastomosis (PCA) are associated with the development of slee p disturbances during the light phase, the neocortical slow-wave activity o f PCA-operated rats was examined with electroencephalography (EEG) 1 month and 6 months after the surgery. The tissue levels of histamine, tele-methyl histamine, 5-hydroxytryptamine (5-HT) (serotonin), and 5-hydroxyindole-3-ac etic acid (5-HIAA) in frontal cortex were assayed by high-performance liqui d chromatography 6 months after the surgery. PCA surgery led to changes in the synchronized, low-frequency, high-amplitude frontal cortex EEG activity recorded during the light phase. Delta-wave amplitude but not delta time w as significantly decreased, whereas both spindle amplitude and spindling ti me were significantly decreased. There were also significant age-related ch anges, presented as increases in the duration of spindles and the amplitude of both delta waves and spindles, PCA-operated rats showed a change in the pattern of EEG activity with increasing age similar to sham-operated rats. This suggests that once established, the resetting of the systems regulati ng the sleep-waking behavior is being maintained with time. The tissue leve ls of both histamine and metabolite in the frontal cortex were increased, w hereas the serotonin system showed only an increase in the level of the met abolite. There was a significant negative correlation between the spindling time and the tissue histamine levels, We suggest that histamine, which par ticipates in the control of vigilance, sleep, and wakefulness, as well as i n the modulation of circadian rhythmicity, may play a role in the developme nt of sleep disturbances in rats with PCA.