CAFFEINE ANTAGONIZES SEVERAL CENTRAL EFFECTS OF DIAZEPAM

In spinal cats, caffeine (3-30 mg/kg i.v.) reduced the increase of dorsal root potentials (DRP) caused by diazepam (0.1-1 mg/kg i.v.) without affecting the prolongation of DRP evoked by phenobarbitone (10-20 mg/kg i.v.). Caffeine antagonized the depression by diazepam, but not that by phenobarbitone, of the ventral root-evoked Renshaw cell discharge. In unrestrained cats, 50 mg/kg caffeine i.p. abolished the elevation induced by 1 mg/kg diazepam i.p. of the threshold for eliciting a rage reaction by stimulation of the lateral hypothalamus but was ineffective against the threshold increase caused by 20 mg/kg phenobarbitone i.p. In the horizontal wire test in mice, caffeine was more potent in reversing the depression of performance induced by diazepam than that by phenobarbitone (ED50 1.8 and 139 mg/kg p.o. (pentos)). The reduction of skeletal muscle tone in mice produced by diazepam was antagonized by low doses of caffeine (ED50 0.53 mg/kg p.o.). While caffeine at low doses (0.3-3 mg/kg p.o.) abolished the anticonflict effect of diazepam in rats, high doses (ED50 160 mg/kg p.o.) were necessary to antagonize the anticonvulsant effect of diazepam on pentylenetetrazole induced seizures in mice. The interaction between caffeine and diazepam is not due to a competition at the benzodiazepine receptors but may involve purinergic mechanisms.