Ro 15-1788 both antagonizes and potentiates adenosine-evoked depression of cerebral cortical neurons

The effects of Ro 15-1788, a benzodiazepine antagonist with some agonist properties, were studied on adenosine and adenosine 5'-N-ethyl-carboxamide (NECA)-evoked depressions of rat cerebral cortical neuronal activity. Iontophoretically applied Ro 15-1788 had both antagonistic and potentiative interactions with adenosine. Reductions in the magnitude of adenosine-evoked depressions of firing were evident during the period of Ro 15-1788 application, with a long-lasting potentiative effect becoming apparent upon termination of the Ro 15-1788 application. Depressions of cell firing evoked by NECA, an uptake-resistant analog of adenosine, were antagonized by Ro 15-1788, with no subsequent potentiation. Larger applications of Ro 15-1788 had a depressant action on neuronal firing, which was antagonized by caffeine (20 mg/kg), an adenosine receptor blocker. These results indicate that Ro 15-1788 may be an antagonist at the adenosine receptor as well as a potentiator of the adenosine response. The prolongation of the adenosine depression is likely to be the result of a persistent inhibition of adenosine uptake by Ro 15-1788. These diverse effects on the adenosine response may account for some of the complex behavioral actions of Ro 15-1788.