Presynaptic dopamine D 2 and muscarine M 3 receptors inhibit excitatory and inhibitory transmission to rat subthalamic neurones in vitro

1 Whole‐cell patch‐clamp recordings were made from subthalamic nucleus (STN) neurones in brain slices from rats. Stimulation with bipolar electrodes evoked synaptic currents mediated by glutamate (EPSCs) and GABA A (IPSCs) receptors. 2 Dopamine reversibly reduced the amplitude of GABA A IPSCs by up to 48% with an IC 50 value of 3.4 ± 0.8 μ m . The dopamine D 2 receptor agonist quinpirole, but not the D 1 receptor agonist SKF 82958, also inhibited GABA A IPSCs. This effect was completely reversed by the D 2 receptor antagonist sulpiride but not by SCH 23390, a D 1 antagonist. 3 Muscarine reversibly reduced the amplitude of GABA A IPSCs by up to 70 % with an IC 50 value of 0.6 ± 0.1 μ m . Inhibition of IPSCs by muscarine was completely blocked by scopolamine (10 μ m ), a muscarinic receptor antagonist. The M 3 muscarinic receptor antagonist 4‐DAMP effectively reversed muscarine‐induced inhibition of IPSCs with an IC 50 of 0.11 ± 0.03 μ m . Although the M 1 receptor antagonist pirenzepine also reversed the inhibition of IPSCs by muscarine, this effect was only observed at relatively high concentrations (IC 50 = 21.7 ± 9.4 μ m ). 4 Dopamine and muscarine both increased the paired‐pulse ratio of GABA A IPSCs. Neither agent produced sustained changes in postsynaptic holding current. 5 Glutamate EPSCs were also inhibited reversibly by dopamine (by up to 29 %; IC 50 = 16 ± 3 μ m ) and muscarine (by up to 41 %; IC 50 = 1.0 ± 0.4 μ m ). However, both agents were more potent and efficacious for reducing GABA IPSCs compared with glutamate EPSCs. 6 These results suggest that the most significant effect of dopamine and muscarine in the STN is to reduce inhibitory synaptic input by acting at presynaptic dopamine D 2 and muscarinic M 3 receptors, respectively.