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 perfor mance liquid chromatography coupled with a fluorometric detector was u sed. K+ (100 mM) depolarization was followed by a 2- to 4-fold increas e in adenosine efflux. The addition of tetrodotoxin (1 muM) to the per fusate was followed by a decrease in spontaneous and K+-evoked adenosi ne efflux. The increase induced by high K+ was markedly inhibited by t he 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), signific antly enhanced the K+-evoked increase in adenosine. The spontaneous ef flux of adenosine was not modified by any of the drugs tested. A neuro toxic lesion of the cholinergic pathway innervating the cortex, althou gh inducing a marked decrease in cortical choline acetyltransferase ac tivity, 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 act ivation.