Up-regulation of brain [3H]diazepam binding sites in chronic caffeine-treated rats.

Brain [3H]diazepam and L-[3H]phenylisopropyladenosine binding sites in caffeine-treated (75 mg/kg/day, i.p. 12 days) and caffeine-withdrawn (30 days) rats were examined. Treatment with caffeine (75 mg/kg/day) for 12 days increases the Bmax (maximum binding capacity) for [3H]diazepam binding by 30.9% whereas the same treatment increased the Bmax for L-[3H]PIA binding by 120%. The Bmax for [3H]diazepam binding sites returns to slightly below control levels but L-[3H]PIA binding sites still remain elevated after 30 days of caffeine withdrawal. The up-regulation of [3H]diazepam binding sites seen in caffeine-treated rats may indicate an interaction between caffeine and benzodiazepines at the receptor level and it may account for the supersensitivity to benzodiazepines seen in behavioral testing.