Abstract
Oxygenated haemoglobin, deoxyhaemoglobin and total blood volume are measured with our recently developed Near-Infrared Spectroscopy [NIRS] apparatus allowing in vivo non invasive real time monitoring of brain metabolism in anaesthetized rats. These measurements are indicative of the state of vascular activity and the state of the oxygen saturation, thus of the level of metabolism in the living tissue. Nicotine is a natural alkaloid derived from tobacco that has been implicated in various effects ranging from addiction to toxic effects and neuro-protective actions. Here we analyse the influence of nicotine as well as that of the non competitive NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate)] upon brain metabolism in anaesthetized rats. In the first 30min after treatment, nicotine decreases significantly although in a transient manner oxygenated haemoglobin and total blood volume while increasing significantly deoxyhaemoglobin. In addition, MK-801 performed in another group of rats was followed by changes in these three parameters that were similar to those monitored in nicotine treated rats. The NIRS methodology appears to be apt to analyzing non-invasively and in real time the influence of systemic pharmacological treatments upon brain metabolism. In particular the data gathered show similarity of action of the two chemicals studied on influencing metabolic brain “behaviour” proposing that their central protective action may pass via the observed similar changes in brain metabolism. These changes could be a common mechanism of adaptation and protection towards neurotoxicity: mechanism that should be also considered in the intent of developing new pharmaceutical approaches for neuro-protective treatments.
Highlights
The pharmacological activities of nicotine have been analyzed in animals and humans since long time
We analyse the influence of nicotine as well as that of the non competitive NMDA receptor antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine maleate)] upon brain metabolism in anaesthetized rats
The central protective action of nicotine is similar to that of the non competitive NMDA receptor antagonist MK-801 [4] as it pass via the defence towards neurotoxicity induced by excitotoxic amino acids as well as beta amyloids present in the senile plaques [5]
Summary
The pharmacological activities of nicotine have been analyzed in animals and humans since long time Nowadays, this natural alkaloid derived from the tobacco has been implicated in toxicity effects but , further to its additive effect it appeared that has nicotine had neuroprotective actions [1]. Nicotine has been used as a prototypical agent for the analysis of drug-induced changes in Functional Magnetic Resonance Imaging [fMRI] in the brain [7,8]. This non invasive methodology is using radio frequency pulses in a strong static magnetic field and is mainly based upon changes in blood flow and delivery of oxygen following neuronal activation.
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