Effect of intracerebroventricular administration of alpha-helical CRH (9-41) on the sleep/waking cycle in rats under normal conditions or after subjection to an acute stressful stimulus.

It has been shown in a previous study that specific lesioning of the noradrenergic system of the locus coeruleus abolished the sleep increase induced by immobilization stress. Given the fact that brain corticotropin-releasing hormone (CRH) acts as a neurotransmitter in the locus coeruleus under stress conditions, the present study was designed to investigate the involvement of CRH in the sleep increase seen after immobilization stress and on the spontaneous wake/sleep cycle. One hundred micrograms of the specific CRH receptor antagonist alpha-helical CRH (9-41), or vehicle alone was injected into the right lateral ventricle 30 min either before subjecting the animals to immobilization stress or before the spontaneous sleep-waking recordings onset. A single intracerebroventricular (i.c.v.) injection of alpha-helical CRH (9-41) had no effect on spontaneous paradoxical sleep but abolished the stress-induced increase, while wakefulness and slow-wave sleep were unchanged under both normal and stressful conditions. We therefore report that the involvement of endogenous CRH in the paradoxical sleep mechanism is dependent on the environmental conditions and suggest that, while the paradoxical sleep increase induced by immobilization stress may be mediated by endogenous corticotropin-releasing hormone, other mechanisms, either CRH-independent or situated at a distance from antagonist activity, may be involved in spontaneous paradoxical sleep. These results show, for the first time, that endogenous CRH may be involved in sleep-waking mechanisms only under stressful conditions and, in particular, as a fundamental component of the paradoxical sleep increase.