ATP AND GLUTAMATE ARE RELEASED FROM SEPARATE NEURONS IN THE RAT MEDIAL HABENULA NUCLEUS - FREQUENCY-DEPENDENCE AND ADENOSINE-MEDIATED INHIBITION OF RELEASE

1. ATP and glutamatergic synaptic currents were compared in slices of rat medial habenula nucleus using whole-cell patch-damp techniques. 2. In most cells low voltage stimulation resulted in glutamatergic respo nses and not purinergic responses. In five cells where ATP currents co uld be stimulated with low voltages, wash out of glutamate antagonists did not reveal evoked glutamate currents. Spontaneous glutamate curre nts confirmed washout of antagonist. 3. Modulation of release probabil ity of glutamate and ATP, assessed by changes in failure rate of synap tic currents, was compared under conditions of different stimulation f requencies and in the presence of adenosine agonists and antagonists. 4. ATP release, but not glutamate release, was shown to be modulated b y increased stimulation frequency which resulted in inhibition of ATP release via A(2)-like adenosine receptors. A(1) receptors caused inhib ition of both ATP and glutamate release. 5. Endogenous adenosine inhib ited glutamate release via A(1) receptors but only inhibited ATP relea se via A(2)-like receptors. 6. Attempts to inhibit the degradation of ATP to adenosine did not alter the frequency dependence of the failure rate. 7. We conclude, from the direct demonstration and from the diff erences in pharmacology and frequency dependence of the modulation of release, that ATP and glutamate responses are due to release from sepa rate neurones.