EFFECTS OF PILOCARPINE OR ARECOLINE ADMINISTRATION ON ACETYLCHOLINE LEVELS AND SEROTONIN TURNOVER IN RAT BRAIN

¹ Laboratory of Chemical Pharmacology, National Heart and Lung Institute, National Institutes of health, Bethesda, Maryland

Despite the similarities between the peripheral muscarinic actions of pilocarpine and arecoline, the central excitatory effect of pilocarpine HCL (100 mg/kg i.p.) lasted several hours in rats and was accompanied by clonic movementS, whereas the excitation induced by arecoline (50 mg/kg i.p.) lasted only 10 minutes and was associated with tremors. The drugs also differed in their biochemical effects on neurotransmitters in the brain. Pilocarpine stimulated the turnover rate of serotonin and approximately doubled the concentrations of acetylcholine, of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and of the dopamine metabolite homovanillic acid. The changes in acetylcholine and 5-HIAA occurred within 0.5 hour and persisted for at least four hours. Arecoline administration also increased acetylcholine and 5-HIAA levels, but the arecoline-induced rise in acetyleholine occurred within five minutes and returned to normal within 20 minutes, well before the 5-HIAA levels began to rise. Prior administration of atropine sulfate (5 mg/kg i.p.), which blocked the overt behavioral and cholinomimetic actions of both drugs, diminished the arecoline-incluced rises in acetylcholine and 5-HIAA levels. However, atropine failed to prevent the pilocarpine-induced rises in acetylcholine and 5-HIAA levels.

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