Chronic caffeine exposure enhances adenosinergic inhibition of cerebral cortical neurons

Chronic administration of caffeine (s.c. for a period of 14 days in escalating doses of 10-70 mg/kg) increased the sensitivity of rat cerebral cortical neurons to the inhibitory action of microiontophoretically applied adenosine. 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. Adenosine sensitivity was determined by the I.T50 method. The I.T50 value for 134 neurons in the caffeine-treated rats of 130.77 +/- 4.33 (S.E.M.) was significantly (P less than 0.001) different to that of 136 neurons in the saline-treated control rats (222.16 +/- 6.68), indicating a supersensitivity to adenosine in neurons which had been chronically exposed to caffeine.