Autoradiographic demonstration of the antagonism of anthramycin and diazepam against cholecystokinin in the mouse brain using the (14C)-2-deoxyglucose method.

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Effects of diazepam (DZP), a synthetic benzodiazepine drug, and anthramycin (ATM), a benzodiazepine antitumor antibiotic produced by a certain species of streptomyces, on the uptake of 2-deoxy-D-(<SUP>14</SUP>C)-glucose (2-DG) in mouse brain neurons with or without cholecystokinin were examined. 2-DG uptake in neurons was evaluated by using an autoradiographic technique. The sulfated octapeptide CCK (CCK8) was injected intracisternally; DZP and ATM, intraperitoneally; and 2-DG, intravenously to mice. Autoradiograms prepared from the slices of the brain were converted to false color images. CCK8 (1 μg/mouse) markedly stimulated the 2-DG uptake in neurons in the various regions of the brain, but the stimulative effects of CCK8 was almost completely suppressed after an intraperitoneal administration of 1.0 mg/kg of DZP or 0.5 mg/kg of ATM. Since it has been previously shown that these doses of DZP and ATM almost completely reversed the antinociception produced by 1 μg/mouse of CCK8, the present results on the 2-DG uptake in the mouse brain are considered to further support the antagonism between CCK8 and DZP or ATM in the central nervous system.
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