Comparative effects of acute and chronic administration of caffeine on local cerebral glucose utilization in the conscious rat

The quantitative 2-[14C]deoxyglucose autoradiographic method was used to compare the effects of acute and chronic administration of caffeine on rat brain energy metabolism. The acute intravenous administration of caffeine (10 mg/kg) to naive rats induced widespread increases in glucose utilization in 20 of 62 structures, mainly in striatal and related areas as well as in the 2 raphe nuclei and the locus coeruleus. After 2 weeks' chronic intraperitoneal injection of caffeine (10 mg/kg), increases in glucose utilization were seen in 6 of 62 structures: the substantia nigra, pars compacta, dorsal raphe, locus coeruleus and the 3 parts of the caudate nucleus. An acute caffeine injection (10 mg/kg) to these chronically caffeine-treated rats induced a further increase in glucose utilization in 9 additional structures but there was no significant difference in the effects of an acute administration of caffeine whether the rats had been chronically pretreated with caffeine or saline. The results of the present study show that brain energy metabolism seems to be subject to only partial tolerance to central stimulation by caffeine.