Chronic caffeine exposure reduces the excitant action of acetylcholine on cerebral cortical neurons

Abstract

Chronic administration of caffeine (s.c. for a period of 14 days in escalating doses of 10–70 mg/kg) decreased the sensitivity of rat cerebral cortical neurons to the excitant action of microiontophoretically applied acetylcholine. The sensitivity of spontaneously firing rat cerebral cortical neurons in caffeine-treated animals was compared with that of saline-treated controls using the same multiple barrel micropipettes tested on the same day. Acetylcholine sensitivity was determined by the E·T 50 method. The E·T 50 for 71 neurons in the caffeine-treated rats of 224.0 ± 11.3 (S.E.M.) was significantly ( P < 0.001) greater than that of 65 neurons in the saline-treated control rats (153.8±6.9), indicating a reduction in the excitant action of acetylcholine on neurons which had been chronically exposed to caffeine. The level of spontaneous activity was also reduced in the caffeine-treated animals. A down-regulation of acetylcholine receptors is a possible cause for these effects.