Histamine-induced arousal in the conscious and pentobarbital-pretreated rat

Histamine has been shown to possess many neurotransmitter-like properties, and a variety of studies indicate that central histamine may function in modulating behavioral arousal. To examine this possibility further, histamine was administered into the lateral cerebral ventricles of the conscious and pentobarbital-anesthetized rat. In the conscious animal, histamine induced a significant increase in spontaneous motor activity which consisted of increased grooming and exploratory behaviors (sniffing, rearing and locomotion) as compared to saline-treated controls. In the pentobarbital-pretreated rat, histamine caused a dose-related decrease in narcosis duration and hypothermia without altering the disposition of pentobarbital in brain or plasma. Administration of compounds structurally related to histamine did not alter spontaneous activity or shorten narcosis duration. While pretreatment with the H2-histamine antagonist, cimetidine, was no effective, H1-histamine antagonists were found to abolish histamine-induced arousal. Administration of haloperidol in doses that significantly attenuated increased spontaneous motor activity by amphetamine did not alter histamine-induced hyperactivity. Likewise, atropine did not significantly alter histamine-induced arousal. These data support the hypothesis that histamine may function in modulating behavioral arousal.