Dose‐dependent effects of the 5‐HT1A receptor agonist 8‐OH‐DPAT on sleep and wakefulness in the rat

Open Access
Publisher Website
Google Scholar
Abstract
SUMMARY 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. Pretreat‐ment 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.