Abstract

Based on the results of independent studies the involvement of norepinephrine in REM sleep regulation was known. Isolated studies showed that the effect could be mediated through either one or more subtypes of adrenoceptors. Earlier we have reported that REM-OFF neurons continue firing during REM sleep deprivation and mild but continuous stimulation of locus coeruleus (LC) or picrotoxin injection into the LC, that did not allow the REM-OFF neurons in the LC to stop firing, reduced REM sleep. However, the mechanism of action and type of adrenoreceptors involved in REM sleep regulation were unknown. The possible mechanism of action has been investigated in this study. It was proposed that if LC stimulation-induced decrease in REM sleep was due to norepinephrine, adrenergic antagonist must prevent the effect. Therefore, in this study, the effects of alpha1, alpha2 and beta-antagonists, viz. prazosin, yohimbine and propranolol, respectively, and alpha2 agonist, clonidine, on LC stimulation-induced reduction in REM sleep were investigated. The results showed that stimulation of LC inhibited REM sleep by reducing the frequency of generation of REM sleep, although the duration per episode remained unaffected. This decrease in the frequency of REM sleep was blocked by beta-antagonist propranolol while the duration of REM sleep per episode was blocked by alpha1-antagonist, prazosin. Also, a critical level of norepinephrine in the system was required for the generation of REM sleep, however, a higher level may be inhibitory. Based on the results of this study and our earlier studies, an interaction between neurons, containing different neurotransmitters and their subtypes of receptors for LC-mediated regulation of REM sleep has been proposed.