1. The effects of electrical stimulation to the round window of the inner ear and caloric vestibular stimulation on the in vivo release of acetylcholine (ACh) from rat hippocampus were investigated, using brain microdialysis coupled with high performance liquid chromatography-electrochemical detection. 2. Hippocampal ACh release was increased to 152% of the basal release by 1-Hz, 200-ms, and 500-microA electrical stimulation to the round window. This effect was dependent on current intensity. 3. Microinjection of 6,7-dinitroquinoxaline-2,3-dione (DNQX) (10 nmol/0.2 microliter), an antagonist of the non-N-methyl-D-aspartate (non-NMDA) type of glutamate receptor, into the medial vestibular nucleus blocked the increase of hippocampal ACh release by electrical stimulation to the round window. In contrast, microinjection of DNQX (10 nmol/0.2 microliter) into the ventral cochlear nucleus did not inhibit the increase of hippocampal ACh release by electrical stimulation to the round window. 4. Electrical stimulation of the round window increased histamine release from the medial septum, which is the origin of the hippocampal cholinergic terminals. However, the depletion of neuronal histamine by alpha-fluoromethylhistidine (100 mg/kg ip) did not suppress the vestibular-evoked release of hippocampal ACh. 5. Although caloric stimulation with water at 37 degrees C did not affect the hippocampal ACh release, the release was increased to 131% of the basal release by caloric stimulation with hot water at 45 degrees C and was also increased to 160% of the basal release by caloric stimulation with ice water, suggesting that the changes in activities of vestibular afferents increased the hippocampal ACh release.(ABSTRACT TRUNCATED AT 400 WORDS)

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.

1. We investigated the effect of unilateral vestibular stimulation on histamine release from the anterior hypothalamic area of urethan-anesthetized rats in vivo, using a brain microdialysis method coupled with high-performance liquid chromatography fluorometry. 2. The histamine release was increased to approximately 180% of the basal release by the electrical stimulation of the inner ear with 1 Hz, 500 microA, and 200 ms for 20 min. This effect was dependent on the current intensity. 3. Activation of the unilateral horizontal semicircular canal by middle ear irrigation for 15 min with 45 degrees C water increased the histamine release to approximately 200% of the basal release. 4. Irrigation of the middle ear with ice water for 15 min increased the histamine release to approximately 190% of the basal release. 5. The histamine release was not changed by the irrigation of the middle ear with 37 degrees C water and the irrigation of the auricle with ice water, which suggests that neither somatosensory stimulation to the middle ear nor nonspecific cold stress affects the histamine release. 6. All these findings suggest that the sensory mismatch signals induced by caloric stimulation and unilateral electrical vestibular stimulation activate the histaminergic neuron system in the brain.

No abstract

Using a microdialysis method, we investigated the effects of the nipecotic acid-induced increase in content of endogenous GABA on in vivo release of histamine from the anterior hypothalamus (AHy) of urethane-anesthetized rats. Nipecotic acid (0.5 mM), an inhibitor of GABA uptake, decreased histamine release to -~60%of the basal level. This effect was partially antagonized by picrotoxin (0.1 mM), an antagonist of GABAA receptors, or phaclofen (0.1 mM), an antagonist of GABAB receptors. These results suggest that histamine release is modulated by endogenous GABA through both GABAA and GABAB receptors. When the tuberomammillary nucleus, where the cell bodies of the histaminergic neurons are localized, was stimulated electrically, the evoked release of histamine from the nerve terminals in the AHy was significantly enhanced by phaclofen, suggesting that GABAB receptors may be located on the histaminergic nerve terminals and modulate histamine release presynaptically. On the other hand, picrotoxin caused an increase in histamine release to~-~1 70% of the basal level, and this increase was diminished by coinfusion with -) -2-amino-5-phosphonopentanoic acid (0.1 mM), an antagonist of NMDA receptors. Previously, we demonstrated tonic control of histamine release by glutamate mediated through NMDA receptors located on the histaminergic terminals in the AHy. These results suggest the possible localization of GABAA receptors on glutamatergic nerve terminals and that the receptors may regulate the basal release of histamine indirectly.