Histamine interaction with the ventral part of the oral pontine tegmentum: its implication in rem sleep modulation

Abstract

Histamine is considered to be strongly involved in wakefulness mechanisms, although some studies have revealed that REM sleep is also sensitive to histaminergic stimulation, thus, suggesting that the histaminergic neurons of the hypothalamic tuberomammilar nucleus would have a descending control over generation of REM sleep pontine mechanisms. The ventral region of the oral pontine reticular nucleus (vRPO ) – an effective region for REM sleep cholinergic generation – has histaminergic innervation. The aim of this work was to examine effects on REM and other sleep–wakefulness states after delivery of small volume histamine microinjections in the vRPO. Five cats with electrodes implanted for chronic sleep polygraphic recordings and with one or two cannulas sterotaxically aimed at the vRPO were used. Histamine microinjections (165 mM, 20–30 nl) in the vRPO and combined experiments with administration of pyrilamide i.p ( H1 antagonist, 1 mg/kg) and intracraneal histamine were performed. Intracraneal saline microinjections and i.p. pyrilamide administration were done as controls. Polygraphic recordings were obtained during 6 h after the different experiments. From the second to the fifth hour post drug NREM and REM sleep significantly decreased and wakefulness and drowsiness significantly increased. Architecture analyses of the sleep–wakefulness cycle (SWC) in this period showed that histamine in the vRPO produced a specific blockage of the transitions from NREM to REM sleep. However, decreased REM sleep and its blockage did not take place early in the first hour after drug; in fact, in some of the animals, histamine in the vRPO produced a rapid entry in REM similar to the one that occurs in narcoleptic episodes. The previous application of pyrilamine blocked the early REM facilitatory effects and the late effects in wakefulness, drowsiness and NREM. Late REM suppression was not blocked by pyrilamide but, since the pyrilamine i.p. alone significantly decreased REM sleep, it was not possible to determine whether or not H1 receptors are involved in the late REM actions of histamine acting in the vRPO. Histamine action in the vRPO has a regulatory role on REM sleep, with early facilitatory effects and a later suppression of this sleep state. H1 receptors seem to be involved in the early REM sleep enhancing effect and in the later modifications of the other SWC states. Supported by FPU 2009-06991 MCYT Grant.