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Effects of selective activation or blockade of the histamine H3 receptor on sleep and wakefulness
J M Monti1, H Jantos, M Boussard
1Department of Pharmacology and Therapeutics, Clinics Hospital, Montevideo, Uruguay.
Abstract:
The effects of the histamine H3 receptor agonist, (R)-alpha-methylhistamine were compared with those of the histamine H3 antagonist, thioperamide, in rats implanted with electrodes for chronic sleep recordings. (R)-alpha-Methylhistamine (1.0-4.0 micrograms) injected bilaterally into the premammillary area where histamine immunoreactive neurons have been detected increased slow wave sleep, whereas wakefulness and REM sleep were decreased. No significant effects were observed when (R)-alpha-methylhistamine (1.0-8.0 mg/kg) was administered i.p. Thioperamide (1.0-4.0 mg/kg i.p.) increased wakefulness and decreased slow wave sleep and REM sleep. Pretreatment with thioperamide (4.0 mg/kg) prevented the effects of (R)-alpha-methylhistamine (2.0 micrograms) on slow wave sleep and wakefulness. Our results further support an active role for histamine in the control of the waking state.
Insights
Histamine plays a key role in regulating wakefulness. A histamine H3 receptor agonist, (R)-alpha-methylhistamine, increased sleep, while an antagonist, thioperamide, promoted wakefulness in rats.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Histamine is a neurotransmitter implicated in regulating sleep-wake cycles.
- The histamine H3 receptor is a key modulator of histaminergic neurotransmission.
Purpose of the Study:
- To investigate the role of histamine in sleep-wake regulation.
- To compare the effects of a histamine H3 receptor agonist and antagonist on sleep architecture in rats.
Main Methods:
- Chronic sleep recordings in rats implanted with electrodes.
- Administration of (R)-alpha-methylhistamine (histamine H3 receptor agonist) and thioperamide (histamine H3 receptor antagonist) via intracerebral or intraperitoneal routes.
- Assessment of sleep parameters including slow wave sleep, wakefulness, and REM sleep.
Main Results:
- Bilateral premammillary injection of (R)-alpha-methylhistamine (1.0-4.0 µg) increased slow wave sleep and decreased wakefulness and REM sleep.
- (R)-alpha-methylhistamine (1.0-8.0 mg/kg) administered intraperitoneally had no significant effect on sleep.
- Intraperitoneal administration of thioperamide (1.0-4.0 mg/kg) increased wakefulness and decreased slow wave sleep and REM sleep.
- Pretreatment with thioperamide blocked the sleep-promoting effects of (R)-alpha-methylhistamine.
Conclusions:
- Histamine actively promotes the waking state.
- The histamine H3 receptor is a critical mediator in histamine's control of the sleep-wake cycle.