Histaminergic Modulation of Hippocampal Acetylcholine Release In Vivo

Abstract

In order to elucidate the modulatory role of the histaminergic neural system in the cholinergic neural system, the acetylcholine release from the CA1 -CA3 region in the hippocampus of anesthetized rats was studied by an in vivo microdialysis method coupled with HPLC-electrochemical detection. The mean value for the basal acetylcholine release was 0.98 2 0.04 pmol/2O min. The acetylcholine release was increased to 172% of the basal level when an electrical stimulation at 200 pA was applied to the tuberomammillary nucleus. An administration of afluoromethylhistidine (1 00 mg/kg i.p.) blocked the electrically evoked release of histamine both from the septal-diagonal band complex and the hippocampus, and abolished the electrically evoked release of acetylcholine from the hippocampus. Zolantidine (5 mg/kg i.p.) attenuated the increase in the electrically stimulated acetylcholine release, but pyrilamine (5 mg/kg i.p.) did not attenuate the increase in the acetylcholine release. These drugs showed no significant effect on the basal acetylcholine release. An administration of (R)-a-methylhistamine (5 mg/kg i.p.) caused a decrease in the acetylcholine release to 48.7% of the basal level, whereas thioperamide (5 mg/kg i.p.) caused an increase in the acetylcholine release 60 min after the injection. These results suggest that the histaminergic system may contribute to the modulation of the activity of the septohippocampal cholinergic system, mainly through H, receptors. Key Words: Acetylcholine-Histamine-Hippocampus-Microdialysis-Thioperamide-Zolantidine.

Endogenous Histamine Facilitates Long-Term Potentiation in the Hippocampus during Walking

“…Stimulation of TMN elicited higher histamine release in the medial septal area than the hippocampus (Mochizuki et al, 1994), likely because of the stronger projection of TMN histaminergic fibers to the medial septal area than the hippocampus (Airaksinen and Panula, 1988;Panula et al, 1989). Thus, we examined whether histaminergic transmission in the medial septum was responsible for the facilitation of basal-dendritic LTP during walking, by means of intraseptal infusion of the H 1 receptor antagonist triprolidine or the H 2 receptor antagonist cimetidine, followed 10 min later by a tetanic stimulation to elicit LTP.…”

“…The activation of hippocampal EEG was likely caused by ACh release in the hippocampus after application of histamine in the medial septum (Bacciottini et al, 2002). Histamine depletion blocked the TMN-stimulated release of histamine from the septal area and ACh release from the hippocampus (Mochizuki et al, 1994). H 1 receptors were reported to mediate the histamineinduced depolarization of septal cholinergic neurons in vitro (Gorelova and Reiner, 1996;Xu et al, 2004), although H 2 receptor activation was reported to be necessary for spontaneous release of ACh, collected in 20 min samples, in the hippocampus in vivo (Bacciottini et al, 2002).…”

Masticatory function and cognitive function

“…Masticatory function may involve inactivation of histamine neurons through the ventromedial hypothalamus and the mesencephalic trigeminal sensory nucleus 75) . The histamine system may contribute to modulate of the activity of the septohippocampal cholinergic system 76) . Hence, the change in acetylcholine release induced by chewing may be a key factor impacting memory processes.…”

Neuropharmacology of Histamine in Brain

“…In vivo, activation of H 2 receptors enhances the release of acetylcholine in the ventral striatum [179], the medial septumdiagonal band complex [245], and the hippocampus [246,247]. The systemic administration of zolantidine, the sole brain-penetrating H 2 receptor antagonist available [248], inhibits acetylcholine release, indicating its facilitation by endogenous histamine [246]. The decrease of ischemic release of dopamine and glutamate by H 2 receptor activation may be a contributing factor in alleviation of neuronal damage in the striatum [249].…”

“…The increase in endogenous acetylcholine release induced in vivo by H 3 receptor antagonists/inverse agonists is due to blockade of autoreceptors, increase in endogenous histamine release, and subsequent activation of H 1 or H 2 receptors [178, 179, 246,247]. Whereas this indirect activation of the cholinergic tone is observed in several brain regions, the opposite modulation has been reported in the amygdala, the increase in acetylcholine release being induced by H 3 receptor agonists [320,321].…”