IN-VIVO REGULATION OF EXTRACELLULAR ADENOSINE LEVELS IN THE CEREBRAL-CORTEX BY NMDA AND MUSCARINIC RECEPTORS

The adenosine concentration in samples of perfusate was determined 24 h after implantation of microdialysis fibre in the cortex. High performance liquid chromatography coupled with a fluorometric detector was used. K+ (100 mM) depolarization was followed by a 2- to 4-fold increase in adenosine efflux. The addition of tetrodotoxin (1 muM) to the perfusate was followed by a decrease in spontaneous and K+-evoked adenosine efflux. The increase induced by high K+ was markedly inhibited by the NMDA receptor antagonist, D(-)-2-amino-7-phosphonoheptanoic acid (1 mM, D-AP7), but not by the muscarinic receptor antagonist, atropine (1.5 muM). The acetylcholine esterase inhibitor, physostigmine (7 muM), and the muscarinic receptor agonist, oxotremorine (100 muM), significantly enhanced the K+-evoked increase in adenosine. The spontaneous efflux of adenosine was not modified by any of the drugs tested. A neurotoxic lesion of the cholinergic pathway innervating the cortex, although inducing a marked decrease in cortical choline acetyltransferase activity, did not significantly modify the cortical adenosine efflux. It is concluded that, under K+-depolarizing conditions, adenosine efflux is triggered by excitatory amino acids and enhanced by muscarinic activation.