Presynaptic GABA(B) and adenosine A₁ receptors regulate synaptic transmission to rat substantia nigra reticulata neurones

1. Patch pipettes were used to record whole-cell currents under voltage clamp in substantia nigra zona reticulate (SNR) neurones in the rat midbrain slice. Bipolar electrodes evoked synaptic currents mediated by glutamate (EPSCs) and GABA(A) receptors (IPSCs). 2. Baclofen reduced the amplitude of IPSCs by 48% at its IC₅₀ value of 0.60 μM. The GABA(B) antagonist CGP 35348 blocked this effect with a K(d) value estimated by Schild analysis of 5 μM. 3. Adenosine reduced IPSCs by 48% at its IC₅₀ value of 56 μM. Adenosine agonists reduced IPSCs with the following rank order of potency: CPA (N⁶-cyclopentyladenosine) > R-PIA (R(-)N⁶(2-phenylisopropyl) adenosine) > CHA (N⁶-cycl ohexyladenosine) = NECA (5'-N-ethylcarboxamidoadenosine) > 2-CADO (2-chloroadenosine) > adenosine. Schild analysis yielded a K(d), value of 0.4 nm for antagonism of CPA by the adenosine A₁ receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine). 4. Both baclofen and adenosine reduced the magnitude of paired-pulse depression of IPSCs, and neither blocked currents evoked by GABA, which was pressure-ejected from micropipettes. 5. Glutamate EPSCs were reduced by baclofen (IC₅₀ = 0.78 μM) and adenosine (IC₅₀ = 57 μM ). Schild analysis yielded a K(d), value of 11 μM for antagonism of baclofen-induced inhibition of EPSCs by CGP 35348. DPCPX (1 μM) completely blocked the inhibitory effects of adenosine (100 μM) and CPA (100 nM) on EPSCs. Neither adenosine nor baclofen reduced inward currents evoked by glutamate which was pressure-ejected from micropipettes. 6. These results show that presynaptic GABA(B) and A₁ receptors reduce glutamate and GABA release from nerve terminals in the SNR.