The effects of the dopamine (DA) receptor agonists apomorphine, bromocriptine and pergolide were compared with those produced by a DA receptor antagonist, haloperidol, in rats implanted with electrodes for chronic sleep recordings. Apomorphine (0.025-2.0 mg/kg) and bromocriptine (0.25-6.0 mg/kg) induced biphasic effects such that low doses decreased wakefulness (W) and increased slow wave sleep (SWS) and REM sleep (REMS), while large doses induced opposite effects. The effects of pergolide (0.05-0.5 mg/kg) on W and SWS were also biphasic, while REMS was suppressed over the range of dosages given. At 0.040 mg/kg, haloperidol increased W, while at 0.160 mg/kg it produced the opposite effect. Pretreatment with haloperidol (0.020 mg/kg) in a dose which preferentially acts at presynaptic sites reversed the effects of low doses of apomorphine, bromocriptine or pergolide on sleep and W. However, the compound differed substantially in its ability to block agonist effects. The increase in sleep after low doses of apomorphine, bromocriptine or pergolide could be related to activation of presynaptic D-2 receptors located on DA axons of mesolimbic and mesocortical systems. In addition, inhibition of norepinephrine and acetylcholine neurons having inhibitory D-2 receptors could contribute to the increase of sleep after small doses of the DA agonists.

No abstract

The effects of midazolam, a short-acting imidazobenzodiazepine, on the sleep cycle of insomniac patients were assessed by means of polygraphic recordings. Baseline placebo nights were compared with drug (30 mg p.o.) and placebo withdrawal nights. The compound was effective in inducing and maintaining sleep on short- and intermediate-term administration. Tolerance was not observed following two weeks of drug use. Subjective reports corroborated the effectiveness of midazolam as a hypnotic. In regard to its effects on sleep stages, midazolam markedly decreased Stage 3 and abolished Stage 4 sleep, while Stage 2 was augmented. REM sleep percentage was not significantly affected. Withdrawal of midazolam was followed by rebound insomnia, in which sleep latency, total wake time and wake time after sleep onset were increased above baseline. Side-effects related to midazolam administration included headache, muscular weakness and dizziness. They were mild and wore off 1-2 hours after awakening.

The histamine synthesis inhibitor a-fluoromethylhistidine (a-FMH, 50 mg/kg, i.p.) significantly reduced wakefulness (W) and light sleep and increased slow wave sleep (SWS) and REM sleep during the light period in rats housed under 12 h light/12 h dark conditions (12L/12D). When animals were housed under 16 h light/8 h dark (16L/8D) they remained awake for a longer period of time during the dark as compared to the 12L/12D lighting cycle. Under this condition a-FMH 50 mg/kg significantly decreased W and increased SWS. Our results tend to indicate that histamine intervenes in sleep-wakefulness regulation. In addition, histamine could be partly involved in the abnormally increased incidence of W observed during the dark in rats housed under 16L/8D conditions.

The actions of diazepam and gamma-hydroxybutyrate (GHB) were assessed on the sleep-wakefulness cycle of male Wistar rats. One and 2 mg/kg diazepam and 12.5 mg/kg GHB had no effects on the sleep variables. After 25 mg/kg GHB, slow wave sleep (SWS2) was significantly increased. Following the combined administration of non-effective doses of GHB and diazepam, significantly higher amounts of SWS2 at the expense of wakefulness were obtained. The injection of a subconvulsant dose of bicuculline (2.5 mg/kg) prior to treatments which significantly increased SWS2 prevented this effect to show up. It is suggested that the actions of GHB and diazepam on the sleep-awake cycle are related to the same neurotransmitter system.