The effects of purinoceptor subtypes on hippocampal extracellular serotonin levels were determined by using in vivo microdialysis. Perfusion with adenosine-5'-triphosphate (ATP) for 20 min produced concentration-dependent changes in hippocampal extracellular serotonin levels, which consisted of an initial rise phase, with levels increasing to 309% of control with 100 mu M ATP, followed by a later rebound reduction phase, with levels decreasing to 6% of control. The P2X(1-7) active P2 purinoceptor agonist, 2-methylthioATP (2-MeSATP: 100 mu M) increased the extracellular serotonin level drastically (638%), while the P2X(1,3) active P2 purinoceptor agonist, alpha,beta-methylene-L-ATP (alpha,beta-meATP: 100 mu M) produced a small increase (132%) in the serotonin level. The P2X(1,2,3,4,5,7) active P2 purinoceptor antagonist, suramin (100 mu M), reduced the basal serotonin level (86%) and the ATP-evoked initial rise phase (from 309 to 254%) without affecting the late reduction phase. The adenosine A(1) receptor antagonist, 8-cyclopentyl-1,3-dimethylxanthine (CPT: 50 mu M) potentiated the rising phase (167%) and abolished the subsequent ATP-evoked reduction phase. Perfusion with CPT and an adenosine A, receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX: 10 mu M), reduced the ATP-evoked initial rise (to 181%) and abolished the late reduction phases of serotonin release. These results indicate that ATP-evoked hippocampal serotonin release is composed of an initial rise phase and a later reduction phase. The ATP-evoked initial rise phase might be produced by an activation of P2X purinoceptor function, whereas the late reduction phase was modulated by the activation of adenosine A(1) receptor function by adenosine, metabolized from ATP in the synaptic cleft. (C) 1999 Elsevier Science Ltd. All rights reserved.
