The action of adenosine on noradrenergic neuronal inhibition induced by stimulation of locus coeruleus

Abstract

Stimulation of locus coeruleus (LC) has been used to induce a noradrenergic inhibition of neurones in the rat cerebral cortex. The local application of adenosine or adenosine monophosphate by microiontophoresis in the cortex was found to produce a reduction of the evoked inhibition if the purine application was begun 20 sec before LC stimulation, but an enhancement of the inhibition if applied up to 35 sec after the LC stimulation. GABA increased the duration of LC inhibition irrespective of time of application. Adenosine and GABA showed no mutual potentiation, but norepinephrine increased the size of responses to both iontophoretic adenosine and GABA. The adenosine-norepinephrine interaction was synergistic, irrespective of the order of application. It is concluded that adenosine may act both presynaptically to inhibit, and postsynaptically to enhance the effects of noradrenergic neurone activation, the dominant effect observed depending on the temporal relationship between LC activation and adenosine application.