Similar increases in extracellular lactic acid in the limbic system duringepileptic and/or olfactory stimulation

Previous studies have shown that physiological stimulation of brain activit y increases anaerobic glucose consumption, both in humans and in experiment al animals. To investigate this phenomenon further, we measured extracellul ar lactate levels within different rat brain regions, using microdialysis. Experiments were performed comparing the effects of natural, physiological olfactory stimulation of the limbic system with experimental limbic seizure s; Olfactory stimulation was carried out by using different odors (i.e. bot h conventional odors: 2-isobutyl-3-methoxypyrazine, green pepper essence; t hymol; and 2-sec-butylthiazoline, a sexual pheromone). Limbic seizures were either induced by systemic injection of pilocarpine (200-400 mg/kg) or foc ally elicited by microinfusions of chemoconvulsants (bicuculline 118 pmol a nd cychlothiazide 1.2 nmol) within the anterior piriform cortex. Seizures i nduced by systemic pilocarpine tripled lactic acid within the hippocampus, whereas limbic seizures elicited by focal microinfusion of chemoconvulsants within the piriform cortex produced a less pronounced increase in extracel lular lactic acid. Increases in extracellular lactate occurring during olfa ctory stimulation with the sexual pheromone (three times the baseline level s) were non-significantly different from those occurring after systemic pil ocarpine. Increases in lactic acid following natural olfactory stimulation were abolished both by olfactory bulbectomy and by the focal microinfusion of tetrodotoxin, while they were significantly attenuated by the local appl ication of the N-methyl-D-aspartate antagonist AP-5. Increases in hippocamp al lactate induced by short-lasting stimuli (olfactory stimulation or micro infusion of subthreshold doses of chemoconvulsants, bicuculline 30 pmol) we re reproducible after a short delay (1 h) and cumulated when applied sequen tially. In contrast, limbic status epilepticus led to a long-lasting refrac toriness to additional lactate-raising stimuli and there was no further inc rease in lactate levels when the olfactory stimulation was produced during status epilepticus. Increases in lactic acid following olfactory stimulatio n occurred with site specificity in the rhinencephalon (hippocampus, pirifo rm and entorhinal cortex) but not in the dorsal striatum. Site specificity crucially relied on the quality of the stimulus. For instance, other natura l stimuli (i.e. tail pinch) produced a similar increase in extracellular la ctate in all brain areas under investigation. The major conclusion of this work is that the presentation of an odor known to be a rat pheromone results in lactate production as great as that induc ed by the systemic convulsant pylocarpine (maximum: 2.286 +/- 0.195 mM and 1.803 +/- 0.108 mM, respectively). This supports the notion that the great magnitude of lactate production known to accompany seizures can result from the intensified neural activity per se ("aerobic gycolysis"), not merely f rom local anoxia or other pathological changes. (C) 2000 IBRO. Published by Elsevier Science Ltd.