Involvement of histaminergic neurons in arousal mechanisms demonstrated with H3-receptor ligands in the cat.
The effects of histamine H3-receptor ligands on sleep-waking parameters were studied in freely moving cats. Oral administration of (R)alpha-methylhistamine (alpha MHA), a H3-agonist, caused a significant increase in deep slow wave sleep while that of thioperamide, a H3-antagonist, enhanced wakefulness in a marked and dose-dependent manner. The arousal effects of thioperamide were prevented by pretreatment with alpha MHA or mepyramine, a H1-receptor antagonist. The findings support the hypothesis that the histaminergic neurons are critically involved in arousal mechanisms and suggest that H3-receptors play an active part in these mechanisms by regulating histamine transmission.
Lin
J S
JS
Département de Médecine Expérimentale, INSERM U52, Université Claude Bernard, Lyon, France.
Sakai
K
K
Vanni-Mercier
G
G
Arrang
J M
JM
Garbarg
M
M
Schwartz
J C
JC
Jouvet
M
M
D000818:Animals; D001143:Arousal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002415:Cats; D004569:Electroencephalography; D005260:Female; D008024:Ligands; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D011968:Receptors, Histamine / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D018100:Receptors, Histamine H3; D012016:Reference Values; D012890:Sleep / Q000187:drug effects
D008024:Ligands; D008761:Methylhistamines; D010880:Piperidines; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; C052075:thioperamide; C048140:N-methylhistamine