EFFECTS OF DIAZEPAM ON ADENOSINE AND ACETYLCHOLINE RELEASE FROM RAT CEREBRAL CORTEX: FURTHER EVIDENCE FOR A PURINERGIC MECHANISM IN ACTION OF DIAZEPAM

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Abstract
Diazepam administered intraperitoneally (0.25 mg/kg) enhanced the rate of efflux of [3H]‐adenosine and its metabolites from rat cerebral cortex. At a lower dose (0.05 mg/kg), this effect could be detected in only one of four rats. Diazepam (0.05 and 0.25 mg/kg i.p.) depressed acetylcholine release from the rat cerebral cortex. Its effect was reversed by theophylline. Theophylline (15 and 30 mg/kg) enhanced acetylcholine release from the rat cerebral cortex. Diazepam (0.25 mg/kg) administered after theophylline failed to cause a reduction in the rate of release, rather there appeared to be a further enhancement of release. Pentobarbitone sodium (5, 10 and 15 mg/kg i.p.) did not elicit any increase in adenosine release. These results support the proposal that benzodiazepines may exert their pharmacological actions by preventing adenosine uptake, thus enhancing the levels of extracellular adenosine.