STUDY OBJECTIVES: Clinical and experimental observations argue that sleep disturbances are common and coexist in patients with epilepsy. Our previous observations have suggested that neural-immune interactions between corticotropin-releasing hormone (CRH) and interleukin-1 (IL-1) are involved in the regulation of physiological sleep-wake behavior. In the present study, we determined the involvement of CRH and IL-1 in the alteration of sleep-wake activities in rats when amygdala kindling was given either at the beginning of the light period (light-onset kindling) or at the beginning of the dark period (dark-onset kindling). DESIGN: The analysis of sleep-wake activities was performed before and after full-blown kindling, and the actions of CRH and IL-1 were tested by pharmacological blockade. SETTING: Neuroscience Laboratory at China Medical University Hospital. PARTICIPANT AND INTERVENTIONS: Male Sprague-Dawley rats were implanted with electroencephalogram (EEG) electrodes and an intracerebroventricular (ICV) guide cannula. Kindling stimuli delivered via a bipolar electrode placing in the right central nucleus of the amygdala. MEASUREMENT AND RESULTS: Amygdala kindling induced diverse effects on sleep. Slow-wave sleep (SWS) and rapid eye movement (REM) sleep decreased during the first 12-hour light period when rats were kindled at light onset. When dark-onset kindling was given, SWS increased but REM sleep was not altered during the first 12-hour dark period. After light-onset kindling, the circulating corticosterone concentrations increased and were blocked by ICV administration of the CRH receptor antagonist, astressin or alpha-hCRH. The ICV administration of the CRH antagonist blocked the light-onset kindling-induced decrease of SWS in a dose-dependent manner. After dark-onset kindling, IL-1 mRNA expression in the hippocampus and cortex increased. The dark-onset kindling-induced SWS was blocked in a dose-dependent manner by ICV administration of IL-1 receptor antagonist (IL-1 ra). The slow-wave activity during SWS was enhanced regardless of when kindling occurred, but both CRH antagonists and IL-1 ra had little effect on the alteration of slow-wave activity. CONCLUSION: These observations argue that amygdala-kindling-induced sleep-wake alterations are modulated by central increases in CRH or IL-1.
