Evidence for histaminergic arousal mechanisms in the hypothalamus of cat.
Polygraphic 23-hr recordings were carried out in 25 adult cats in order to examine the effects of both systemic and local injections of various histaminergic and antihistaminergic drugs on sleep-waking cycles. alpha-Fluoromethylhistidine (alpha-FMH), a specific inhibitor of histidine decarboxylase, when injected intraperitoneally at a dose of 20 mg/kg, induced a significant increase in deep slow wave sleep (S2) and a decrease in wakefulness (W), without modifying light slow wave sleep (S1) and paradoxical sleep (PS). Intraperitoneal injections of mepyramine (1 mg and 5 mg/kg), a well-known histamine H1-receptor antagonist, increased deep slow wave sleep and decreased wakefulness, as well as paradoxical sleep. Bilateral injections of alpha-FMH (50 micrograms/1 microliter) into the ventrolateral posterior hypothalamus, where histamine immunoreactive neurones have been recently identified, resulted in a significant decrease in wakefulness and increase in deep slow wave sleep. Similarly, injections of mepyramine (120 micrograms/1 microliter) in the same structures caused a significant decrease in wakefulness and an increase in deep slow wave and paradoxical sleep as well. In contrast, local injections of SKF-91488 (50 micrograms/1 microliter), a specific inhibitor of histamine-N-methyltransferase, led to a significant increase in wakefulness and decrease in both slow wave sleep (SWS) and paradoxical sleep. Injections of histamine, at doses of 5, 30 and 60 micrograms/1 microliter, also increased wakefulness and decreased slow wave sleep dose dependently, while these effects were completely blocked by pretreatment with mepyramine. The results suggest that histaminergic systems in the hypothalamus play an important role in arousal mechanisms and their actions are mediated through H1-receptors.
Lin
J S
JS
Département de Médicine Expérimentale, INSERM U52, CNRS UA 1195, Université Claude Bernard, Lyon, France.
Sakai
K
K
Jouvet
M
M
D000818:Animals; D001143:Arousal / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D017259:Dimaprit / Q000031:analogs & derivatives*; D005260:Female; D006632:Histamine / Q000494:pharmacology / Q000502:physiology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors; D007031:Hypothalamus / Q000502:physiology*; D007034:Hypothalamus, Posterior; D007267:Injections; D007274:Injections, Intraperitoneal; D008297:Male; D008762:Methylhistidines / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D013890:Thiourea / Q000494:pharmacology
D006633:Histamine Antagonists; D008762:Methylhistidines; C024535:SK&F 91488; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D006640:Histidine Decarboxylase; D013890:Thiourea; D011738:Pyrilamine; D017259:Dimaprit