Dopamine D-1-like receptor-mediated presynaptic inhibition of excitatory transmission onto rat magnocellular basal forebrain neurones

1. Excitatory postsynaptic currents (EPSCs) following focal afferent stimulation were recorded from patch-clamped magnocellular neurones in a thin-slice preparation of the rat basal forebrain. Evoked EPSCs had a mean decay time constant of 3.81 +/- 0.09 ms and were reversibly blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5 mu M). 2. Bath-applied dopamine (DA) reduced evoked EPSC amplitude by up to 54.2 +/- 2.3% with an IC50 of 19.9 mu M in normal Krebs solution (2.5 mM Ca2+, 1.2 mM Mg2+) without effect on postsynaptic holding current. 3. DA (30 mu M) reduced the mean frequency of spontaneous miniature EPSCs recorded in 0.5 mu M tetrodotoxin without affecting their mean amplitude, rise time or decay time constant. This effect was diminished by 100 mu M Cd2+. 4. The effect of DA on evoked EPSCs was mimicked by the D-1-like receptor agonist, SKP 81297 (IC50 25.6 mu M), but not by the D-2-like receptor agonist R(-)-TNPA (30 mu M) or (-)-quinpirole (30 mu M), and was antagonized by the D-1-like receptor antagonist R(+)-SCH 23390 (estimated dissociation constant K-B = 1.7 mu M) but not by the D-2-like receptor antagonist S(-)-eticlopride (10 mu M). 5. Forskolin (10 mu M) reduced evoked EPSCs to approximately 60% of the control amplitude, and occluded the effect of subsequent application of DA. 6. These results suggest that glutamatergic afferents to magnocellular basal forebrain neurones possess presynaptic D-1-like DA receptors, and that activation of these receptors reduces excitatory glutamatergic transmission, probably via an adenylyl cyclase-dependent pathway.