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

Brain [3H]diazepam and [3H]L-phenylisopropyladenosine binding sites in caffeine treated (75 mg/kg/day, i.p. 12 days) and caffeine withdrawn (30 days) rats were examined.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 increases the Bmax for [3H]L-PIA binding by 165%. The Bmax for [3H]diazepam binding sites returns to slightly below control levels but [3H]L-PIA binding sites remain elevated after 30 days of caffeine withdrawal. These findings suggest that the up-regulation of [3H]diazepam binding sites seen in caffeine treated rats may not be adequately explained by a direct antagonism of caffeine on benzodiazepine receptors. Other modes of interaction therefore must be considered.