We have previously reported that the spontaneous release of [3H]5-hydroxytryptamine(5-HT) was markedly decreased by hypoxic insult in rat hippocampal slices. In the present study, the effect of glucose on 5-HT release was examined. Fractional release of [3H]5-HT was measured from an incubation medium exchanged every 10 min for 140 min and after stabilization of [3H]5-HT release, 10 or 20 min period of hypoxia was induced by exchanging the media which have been previously saturated by 95% N2/5% CO2 gas. In the media containing 1, 2, 5, 10 or 20 mM glucose, [3H]5-HT release was stabilized after 40 min of incubation. Exposure to hypoxia decreased [3H]5-HT release up to 60% of the control level in a glucose concentration-dependent manner and recovered gradually after hypoxic periods. However, in the media containing no glucose, the spontaneous release of [3H] 5-HT increased continuously during incubation. Moreover, when hippocampal slices were exposed to hypoxia, the [3H]5-HT release increased up to 150% of the control level and recovered gradually to the control level after hypoxic periods. These results demonstrate that hypoxia inhibits or enhances 5-HT release in the presence or absence of extracellular glucose respectively and suggest that the availability of extracellular glucose is a key factor to determine the direction of 5-HT release under hypoxic condition.
Animal ; Cell Hypoxia ; Dose-Response Relationship, Drug ; Glucose/*pharmacology ; Hippocampus/*secretion ; In Vitro ; Male ; Rats ; Rats, Sprague-Dawley ; Serotonin/*secretion

AIMTo determine whether serotonin, a major neurotransmitter in brain, can modulate the production of secretory beta-amyloid protein precursor (sAPP) by activation of serotonin 5-HT2C receptor.

METHODSThe hippocampal slices of rats were incubated with various concentrations of serotonin, M-110, or L-107. sAPP released into the incubation medium were assayed by Western blot analysis assay with monoclonal antibody 22C11 for 2 h.

RESULTSVarious concentrations of serotonin (1.0 x 10(-2) - 1.0 x 10(3) micromol x L(-1)), M-110, a serotonin 5-HT2C agonist (1.5 x 10(-6) - 1.5 x 10(3) micromol x L(-1)), showed positive effect on the production of sAPP while L-107, a serotonin 5-HT2C antagonist (1.0 x 10(-9) - 1.0 x 10(3) micromol x L(-1)), showed negative effect on the production of sAPP over controls.

CONCLUSIONSerotonin modulates production of secretory amyloid beta-protein precursor through serotonin 5-HT2C receptor in incubated rat hippocampal slices.

Amyloid beta-Protein Precursor ; secretion ; Animals ; Hippocampus ; metabolism ; In Vitro Techniques ; Male ; Peptide Fragments ; secretion ; Rats ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT2C ; Serotonin ; pharmacology ; Serotonin 5-HT2 Receptor Agonists ; Serotonin 5-HT2 Receptor Antagonists

BACKGROUNDAnatomic and electrophysiological studies have revealed that the neurons located in the media vestibular nuclei (MVN) receive most of the sensory vestibular input coming from the ipsilateral labyrinth and the responses of MVN neurons to caloric stimulation directly reflect changes in primary vestibular afferent activity. The aim of this study was to clarify the intrinsic characteristics of serotonin (5-hydroxytryptamine, 5-HT) release in the MVN during the period of vertigo induced by caloric stimulation.

METHODSWe used an in vivo microdialysis technique to examine the effects of caloric stimulation on the serotoninergic system in MVN. Twenty four guinea pigs were randomly divided into the groups of irrigation of the ear canal with hot water (n = 6), ice water (n = 6) and 37 degrees C water (n = 4), and the groups of irrigation of the auricle with hot water (n = 4) and ice water (n = 4), according to different caloric vestibular stimulation. We examined the animal's caloric nystagmus with a two-channel electronystagmographic recorder (ENG), and meanwhile examine serotonin (5-hydroxytryptamine, 5-HT) level in the MVN with microdialysis technique after caloric stimulation.

RESULTSIn the caloric test the hot water (44 degrees C) irrigation of the right external auditory canal induced horizontal nystagmus towards the right side lasting about 60 seconds and the ice water irrigation of the right external auditory canal induced it towards the left side lasting for about 90 seconds. No nystagmus was induced by 37 degrees C water irrigation of the external ear canal. Therefore, it was used as a negative control stimulation to the middle ear. The MVN 5-HT levels significantly increased in the first 5-minute collecting interval and increased to 254% and 189% of the control group in the second collecting interval in response to caloric vestibular stimulation with ice water and hot water respectively. The serotonin release was not distinctly changed by the irrigation of the auricle with ice water or hot water.

CONCLUSIONSNeither somato-sensory stimulation of the middle ear nor nonspecific cold or hot stress affects the serotonin release. The rise of 5-HT in MVN may be involved in the mechanism of vertigo induced by caloric stimulation.

Animals ; Caloric Tests ; Guinea Pigs ; Microdialysis ; Serotonin ; secretion ; Vertigo ; etiology ; Vestibular Nuclei ; pathology