Changes in Motor Activity and Acetylcholine Turnover Induced by Lidocaine and Cocaine in Brain Regions of Rats

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Consistent with prior findings in other animals, lidocaine and cocaine, 50–100 mg/kg, subcutaneously, produced dissimilar behavioral effects in rats in this study. Lidocaine induced sedation, while cocaine increased motor activity 12-fold, compared with saline solution. To determine whether the dissimilar behavioral effects were related to differences in acetylcholine turnover rates with the two local anesthetics, the authors infused deuterated phosphorylcholine intravenously for 9 min beginning 30 min after subcutaneous injections of saline solution, lidocaine, 100 mg/kg, or cocaine, 100 mg/kg, in other groups of rats. Rats were then killed by microwave irradiation focused to the head. Acetylcholine and choline concentrations in several brain structures were measured by gas chromatography-mass fragmentography. Principles of steady-state kinetics were applied to estimate the fractional rate constant of acetylcholine efflux and turnover rate of acetylcholine from the incorporation of deuterium into choline and acetylcholine. Lidocaine and cocaine did not change the steady-state concentrations of acetylcholine or choline. Lidocaine decreased the acetylcholine turnover rate (24 per cent) in the cerebral cortex, whereas cocaine increased the acetylcholine turnover rate (29 per cent) in the cerebral cortex and the diencephalon (58 per cent), but not in the caudate nucleus or the hippocampus. These results suggest that the dissimilar behavioral effects induced by the local anesthetics lidocaine and cocaine may have been associated with concomitant changes in acetylcholine utilization in the cortex of the rat brain.

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