Effects of oxolinic acid on the sleep-wakefulness cycle of the rat.

Abstract

1 A study was carried out in rats (prepared for chronic sleep recording) of the effects of oxolinic acid on the sleep-wakefulness cycle.2 In addition, the actions of oxolinic acid on the sleep-wake cycle were assessed after pretreatment with drugs interfering with central catecholamine mechanisms or facilitating central gamma-aminobutyric acid (GABA) activity.3 Oxolinic acid (8-32 mg/kg) induced a significant and dose-related increase of waking EEG, while slow wave and REM sleep were decreased.4 The effects of oxolinic acid on waking, slow wave and REM sleep were antagonized by alpha-methyl-p-tyrosine (50-100 mg/kg) which interferes with the synthesis of catecholamines.5 FLA-63 (25 mg/kg) which is a specific inhibitor of noradrenaline synthesis, was effective in blocking oxolinic acid-related increase of waking and decrease of slow wave sleep.6 Haloperidol (0.4-0.6 mg/kg) which blocks central dopamine and noradrenaline receptors, reversed oxolinic acid-induced actions on waking and slow wave sleep. Spiroperidol (2-4 mg/kg) which interferes with dopamine and 5-hydroxytryptamine mechanisms, only antagonized the effect of oxolinic acid on light slow wave sleep. REM sleep was further decreased by both neuroleptic agents.7 gamma-Hydroxybutyrate (25-50 mg/kg), which acts as a GABA agonist and amino-oxyacetic acid (20 mg/kg), which considerably increases central GABA levels, were ineffective in blocking oxolinic acid-related disruption of the sleep-wake cycle.8 Our results suggest that the catecholamines are involved in the arousing effect of oxolinic acid.