Inhibitory action of CGS 21680 on cerebral cortical neurons is antagonized by bicuculline and picrotoxin—is GABA involved?

Abstract

The possibility of an involvement of endogenously released GABA in the inhibitory actions of A 1 and A 2a adenosine receptor agonists on rat cerebral cortical neurons discharges was examined using the GABA A antagonists bicuculline and picrotoxin. The A 1 agonist N 6-cyclopentyladenosine (CPA), the A 2a agonist CGS 21680 and the non-selective receptor agonist, adenosine, depressed neuronal firing. Applications of bicuculline or picrotoxin enhanced the spontaneous firing rate of cortical neurons, indicating the presence of ongoing GABA-ergic inhibition. Antagonism of GABA A receptors blocked the depressant effects of CGS 21680 on neuronal firing; was without effect on CPA-evoked inhibitions and tended to reduce the duration of adenosine-evoked inhibitions. These results suggest that the depressant effects of A 2a receptor activation are due to an increase in GABA-ergic inhibition, likely as a consequence of increased GABA release. GABA does not appear to be involved in adenosine A 1 receptor-mediated inhibition of neuronal firing.