CHANGES IN EXTRACELLULAR ADENOSINE DURING CHEMICAL OR ELECTRICAL BRAIN-STIMULATION

The purpose of this study was to determine the changes in adenosine an d adenosine metabolites during graded electrical stimulation or kainic acid-induced activation and to assess the role of adenosine in the ce rebral blood flow (CBF) response to increased brain activity. A modifi ed brain microdialysis technique was used to sample cerebral interstit ial fluid (ISF), deliver drugs locally to the brain, electrically stim ulate the brain, and measure local CBF (H2 clearance). Microdialysis p robes were implanted bilaterally in the caudate nuclei of ketamine-ane sthetized rats. Graded electrical stimulation at 5, 15, and 30 Hz incr eased dialysate adenosine 1.5-fold, 2.3-fold, and 4.7-fold, respective ly. Local infusion of kainic acid, an agonist of the excitatory amino acid neurotransmitter glutamate, produced a transient increase (2-fold ) in dialysate adenosine and sustained increases in dialysate inosine (2-fold), hypoxanthine (4-fold) and CBF (2.4-fold). When the adenosine receptor antagonist 8(p-sulphophenyl)-theophylline (SPT, 10(-3) M) wa s co-administered with kainic acid, CBF increased only 1.6-fold, while the increase in dialysate adenosine was augmented by 40%. These data demonstrate that ISF adenosine increases during brain activation and s uggest that adenosine contributes to active hyperemia in the brain.