Dose‐dependent effects of the 5‐HT_1A receptor agonist 8‐OH‐DPAT on sleep and wakefulness in the rat

Abstract

SUMMARY Sleep and wakefulness were studied in rats following administration of a selective 5-HTIA agonist (&OH-DPAT), a non-selective 5-HTl, antagonist [( -) pindolol] and a combination of 8-OH-DPAT and (-) pindolol. 8-OH-DPAT (1.0-4.0 pg) injected into the dorsal raphe nucleus increased slow-wave sleep and decreased wakefulness. Administration of the 5-HT,, agonist by subcutaneous route induced biphasic effects such that low doses (0.010 mg kg-I) decreased wakefulness and increased slow-wave sleep while higher doses (0.375 mg kg-I) induced opposite effects. REM sleep was suppressed and REM latency was increased, what could be tentatively ascribed to a non-specific effect (hypothermia). ( -) Pindolol (1.0-4.0 mg kg-I) induced an initial increase of wakefulness and a decrease of NREM sleep and REM sleep. Thereafter, NREM sleep showed a marked increase while REM sleep remained depressed. Pretreatment with (-) pindolol reversed the effects of both small and large doses of 8-OH-DPAT on slow-wave sleep and wakefulness.The opposite effects, observed on the waking EEG after activation of either serotonin autoreceptors or postsynaptic 5-HTI, receptors with adequate doses of g-OH-DPAT, tend to indicate an active role for the 5-HTIA receptor in the control of the waking state.

Neurobiological mechanisms for the regulation of mammalian sleep–wake behavior: Reinterpretation of historical evidence and inclusion of contemporary cellular and molecular evidence

“…These pharmacological results suggest that serotonin may suppress the activity of hypothalamocortical and basalo-cortical wake-promoting systems. Conversely, a number of other pharmacological studies utilizing various agonists and antagonists of different types of 5-HT receptors and 5-HT1A receptor knock-out mice suggest 5-HT may be involved in maintaining wakefulness (Bjorvatn et al, 1997;Boutrel et al, 2002;Dugovic et al, 1989;Dzoljic et al, 1992;Monti and Jantos, 1992;Ponzoni et al, 1993;Ursin, 1976;Wojcik et al, 1980). Thus, after reviewing the existing evidence, we suggest that serotonergic cells in the RN may participate in both wakefulness and SWS with processes yet to be elucidated.…”

The involvement of serotonin receptors in suanzaorentang-induced sleep alteration

“…It has been proposed that 5-HT 1A receptor agonist may influence wakefulness, NREMS and REMS depending on the dose and agonist used [36][37][38]. Nevertheless, the biphasic effect of serotonin on sleep-wake regulation may be due to the fact that serotonin can act at distinct brain regions that involve the control of sleep-wake activity, and that of different distributions of different 5-HT receptor subtypes in the brain [39].…”

Neuropharmacology of Sleep and Wakefulness

“…Systemic administration of agonists for 5HT 1A , 5HT 1B , 5HT 2A/2C or 5HT 3 receptors causes an increase in wakefulness and a decrease in sleep (reviewed in75). Local administration of a 5HT 1A receptor agonist to the dorsal raphé nucleus increases wakefulness in rat76 but increases REM sleep in cat 77. Microinjection of a 5HT 2A/2C receptor agonist into rat dorsal raphé nucleus also decreases REM sleep with no significant effect on wakefulness 78.…”