Dose-dependent effects of the 5-HT1A receptor agonist 8-OH-DPAT on sleep and wakefulness in the rat.
Sleep and wakefulness were studied in rats following administration of a selective 5-HT1A agonist (8-OH-DPAT), a non-selective 5-HT1A antagonist [(-) pindolol] and a combination of 8-OH-DPAT and (-) pindolol. 8-OH-DPAT (1.0-4.0 µg) injected into the dorsal raphe nucleus increased slow-wave sleep and decreased wakefulness. Administration of the 5-HT1A agonist by subcutaneous route induced biphasic effects such that low doses (0.010 mg kg-1) decreased wakefulness and increased slow-wave sleep while higher doses (0.375 mg kg-1) 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-1) 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-HT1A receptors with adequate doses of 8-OH-DPAT, tend to indicate an active role for the 5-HT1A receptor in the control of the waking state.
Monti
JM
Department of Pharmacology and Therapeutics, School of Medicine, Clinics Hospital, Montevideo, Uruguay.
Jantos
H