The effects of nicotine on the activity of different dehydrogenases in frontoparietal regions and subcortical nuclei of the rat brain have been studied using histochemical methods. Nicotine sulphate was intraperitoneally administered in acute (4 mg/kg/day × 3 days) or chronic (ALZET osmotic pump providing 2 mg/kg/day × 15 days) doses. The enzymes analyzed were glyceraldehyde‐3‐phosphate, lactate, malate and succinate dehydrogenases (gly3PDH, LDH, MDH, and SDH, respectively). The results demonstrate that chronic as well as acute administration of nicotine produced strong increases in all these enzymatic activities in the superior layers (I, II and III) of the frontoparietal cortex (cingulate, motor and somatosensory regions); but high increases were not seen in the deeper layers of the cortex or in the subcortical nuclei (substantia nigra, caudate‐putamen, nucleus accumbens or nucleus basalis magnocellularis). These hyperactivities were produced in brain regions with normally low enzymatic activity (cortex), but not in those with great intensity (subcortical nuclei). The results are in rough agreement with previous reports on nicotine‐induced increases in glucose utilization, gly3PDH genic expression and neuronal hyperactivity in the brain cortex; but significant discrepancies between the cortical enzymatic maps and those obtained both in these studies and others on nicotine(N)‐receptor localization have been appreciated. The results support the hypothesis that nicotinic cholinergic drugs can have metabolic, long‐lasting stimulant effects on cortical neurons at specific points (probably layer III pyramidal cells and structures with α7‐N‐receptors) of the cortical circuits that could be of great interest in improving altered cognitive functions that are present in Alzheimer disease, as well as in other less severe mental disturbances. Mitochondrial hyperfunction should also be evaluated as a possible side‐effect (as an oxidative stress inductor) of these kinds of drugs. J. Neurosci. Res. 64:626–635, 2001. © 2001 Wiley‐Liss, Inc.

Glyoxylic acid is synthesized and catabolized in cells of vertebrates; several pathways have been described. In previous papers, we have demonstrated the localization in some areas of the rat cerebral cortex both of beta-NAD-dependent glyoxylate dehydrogenase (glyoDH), using an enzymohistochemical method, and of glyoxylate-complex molecules, using immunocytochemical procedures. In this study we have applied these two techniques in various areas of the prefrontal cortex with different histological cytoarchitecture. GlyoDH has been located in most neurons, in some glial cells, and in capillary wall structures in all cortical layers of all areas of the rat prefrontal cortex. Antibodies against glyoxylate-complex molecules showed positive immunoreactivity in scattered neurons, mostly of multipolar or stellate appearance, from layers III, IV, and V in the medial precentral area, but not in cortical areas 24, 25, or 32 of the prefrontal cortex. Immunoreaction was found in the periphery of neuronal perikarya and in some of their processes. These results demonstrate the existence of a particular area-dependent neuronal cortical system, of specific but uncertain function, related to glyoxylic acid and/or glyoxylate compounds. At the electron microscope level, positive reaction was associated with synaptic sites, axonal filaments, glial cells, and several components of the blood-brain barrier. These localizations suggest the involvement of glyoxylate derivatives in synaptic functioning and also in glial cell functions.

No abstract