Basal Forebrain Histaminergic Transmission Modulates Electroencephalographic Activity and Emergence from Isoflurane Anesthesia

The tuberomammillary histaminergic neurons are involved in the sedative component of anesthetic action. The nucleus basalis magnocellularis (NBM) in the basal forebrain receives dense excitatory innervation from the tuberomammillary nucleus and is recognized as an important site of sleep-wake regulation. This study investigated whether NBM administration of histaminergic drugs may modulate arousal/emergence from isoflurane anesthesia. Microinjections of histaminergic agonists and antagonists were made into the NBM of rats anesthetized with isoflurane. The changes in electroencephalographic activity, including electroencephalographic burst suppression ratio and power spectra, as well as respiratory rate, were recorded under basal conditions and after NBM injection. Time to resumption of righting reflex was recorded as a measure of emergence from anesthesia. The rats displayed a burst suppression electroencephalographic pattern at inhaled isoflurane concentrations of 1.4-2.1%. Application of histamine (1 microg/0.5 microl) to the NBM reversed the electroencephalographic depressant effect of isoflurane; i.e., electroencephalographic activity shifted from the burst suppression pattern toward delta activity at 1.4% isoflurane, and the burst suppression ratio decreased at 2.1% isoflurane. Histamine-evoked activation of electroencephalography was blocked by NBM pretreatment with a H1 receptor antagonist, triprolidine (5 microg/1 microl), but not by a H2 receptor antagonist, cimetidine (25 microg/1 microl). The respiratory rate was significantly increased after histamine injection. NBM application of histamine facilitated, while triprolidine delayed, emergence from isoflurane anesthesia. Histamine activation of H1 receptors in the NBM induces electroencephalographic arousal and facilitates emergence from isoflurane anesthesia. The basal forebrain histaminergic pathway appears to play a role in modulating arousal/emergence from anesthesia.