PRESYNAPTIC GABA(B) AND ADENOSINE A(1) RECEPTORS REGULATE SYNAPTIC TRANSMISSION TO RAT SUBSTANTIA-NIGRA RETICULATA NEURONS

1. Patch pipettes were used to record whole-cell currents under voltag e clamp in substantia nigra zona reticulate (SNR) neurones in the rat midbrain slice. Bipolar electrodes evoked synaptic currents mediated b y glutamate (EPSCs) and GABA(A) receptors (IPSCs). 2. Baclofen reduced the amplitude of IPSCs by 48% at its IC50 value of 0.60 mu M. The GAB A(B) antagonist CGP 35348 blocked this effect with a K-d value estimat ed by Schild analysis of 5 mu M. 3. Adenosine reduced IPSCs by 48% at its IC50 value of 56 mu M. Adenosine agonists reduced IPSCs with the f ollowing rank order of potency: CPA (N-6-cyclopentyladenosine) > R-PIA (R(-)N-6-(2-phenylisopropyl)adenosine) > CHA (N-6-cyclohexyladenosine ) = NECA (5'-N-ethylcarboxamidoadenosine) > 2-CADO (2-chloroadenosine) > adenosine. Schild analysis yielded a K-d value of 0.4 nM for antago nism of CPA by the adenosine A(1) receptor antagonist DPCPX (8-cyclope ntyl-1,3-dipropylxanthine). 4. Both baclofen and adenosine reduced the magnitude of paired-pulse depression of IPSCs, and neither blocked cu rrents evoked by GABA, which was pressure-ejected from micropipettes. 5. Glutamate EPSCs were reduced by baclofen (IC50 = 0.78 mu M) and ade nosine (IC50 = 57 mu M) Schild analysis yielded a K-d value of 11 mu M for antagonism of baclofen-induced inhibition of EPSCs by CGP 35348. DPCPX (1 mu M) completely blocked the inhibitory effects of adenosine (100 mu M) and CPA (100 nM) on EPSCs. Neither adenosine nor baclofen r educed inward currents evoked by glutamate which nias pressure-ejected from micropipettes. 6. These results show that presynaptic GABA(B) an d A(1) receptors reduce glutamate and GABA release from nerve terminal s in the SNR.