Histochemical study of acute and chronic intraperitoneal nicotine effects on several glycolytic and Krebs cycle dehydrogenase activities in the frontoparietal cortex and subcortical nuclei of the rat brain

Abstract

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.

Glutamatergic and GABAergic Metabolism in Mouse Brain under Chronic Nicotine Exposure: Implications for Addiction

“…However, a very recent study conducted in awake rats indicated a significant reduction in neuronal glucose oxidation and neurotransmitter cycle flux with 0.7 mg/kg nicotine exposure [45]. The effects of nicotine on the activity of various glycolytic and TCA cycle enzymes have been studied under acute and chronic nicotine treatments in frontoparietal regions and subcortical nuclei of the rat brain [26]. Both acute as well as chronic exposure of nicotine increases enzymatic activities in the frontoparietal cortex but deeper layers of the cortex, substantia nigra, caudate-putamen, nucleus accumbens or nucleus basalis magnocellularis did not exhibit increase in activity as high as seen in the frontoparietal cortex.…”

“…Mice were divided into three groups: Group (i) mice treated with normal saline (0.9% NaCl) (n = 6), Group (ii) mice treated with 0.5 mg/kg nicotine (n = 6, sc), Group (iii) mice treated with 2.0 mg/kg nicotine (n = 6, sc). Nicotine dose was selected based on previous studies where nicotine, 0.1 to 4 mg/kg, has been used in different experimental paradigms [25], [26], [32], [33], [34], [35], [36]. Mice in Group (ii) and (iii) received nicotine hydrogen tartrate (SIGMA, 0.1 ml, sc) at a dose of 1.4 and 5.7 mg/kg body weight, which is equivalent to 0.5 and 2 mg/kg nicotine free base, 3 times a day every 8 h for 4 weeks.…”

“…Animal studies have revealed an increase in local cerebral glucose utilization [24], cerebral blood flow and oxygen consumption during acute nicotine administration [25]. Acute and chronic nicotine exposure increased the expression of enzymes involved in glycolysis and Kreb’s cycle [26]. However, the implication of increased enzymatic activity upon nicotine exposure on the cerebral metabolism remains to be evaluated.…”

FTIR microspectroscopic analysis of the effects of certain drugs on oxidative stress and brain protein structure

“…The nicotine dose administered was the same as that used in previous work showing it to be responsible for dehydrogenase activation and NGF induction, but not the induction of apoptosis. 13,14 We have previous information on the minimum amphetamine dose inducting apoptosis in the hippocampus using a similar treatment schedule as here. Here, the selected dose was 75% lower than in that study in order to prevent apoptosis.…”

“…Some of the effects of this drug are positive, such as neuroprotection against neurotoxic agents, ageing, and pathological situations. [6][7][8][9][10][11][12] Our research group has demonstrated that nicotine increases the turnover of the glycolytic pathway and Krebs cycle in neurons, 13 and the NGF immunoreactivity in the frontoparietal cortex. 14 The benefits of other changes, such as the modification of synaptic transmission 15 and the activation of the midbrain dopamine system, 16 are more debatable.…”