CHARACTERIZATION OF DOPAMINE-RECEPTORS MEDIATING INHIBITION OF EXCITATORY SYNAPTIC TRANSMISSION IN THE RAT HIPPOCAMPAL SLICE

1. The effect of dopamine (DA) on the excitatory synaptic transmission was studied in the CA1 neurons of rat hippocampal slices using intrac ellular recording technique. 2. Depolarizing excitatory postsynaptic p otentials (EPSPs) were evoked by stimulation of the Schaffer collatera l-commissural pathway. Superfusion of DA (0.03-1 mu M) reversibly decr eased the EPSP in a concentration-dependent manner and with an estimat ed IC50 of 0.3 mu M. The sensitivity of postsynaptic neurons to the gl utamate-receptor agonists, lpha-amino-3-hydroxy-5-methylisoxazole-4-pr opionic acid or N-methyl-D-aspartate was unchanged by DA (0.3 mu M) pr etreatment. In addition, DA (0.3 mu M) increased the magnitude of pair ed-pulse facilitation, a phenomenon attributed to an increase in the a mount of transmitter released in response to the second stimulus. 3. T he reduction of DA (0.3 mu M) on the EPSP was antagonized by sulpiride (1-10 nM), a selective D-2-receptor antagonist. However, D-1-receptor antagonist, SKF-83566 (1-10 mu M), did not significantly affect the r eduction of DA (0.3 mu M) on the EPSP. 4. -2-(N-Phenylethyl-N-propyl)a mino-5-hydroxytetralin (1 mu M), an agonist of D-2 receptor, mimicked the inhibitory effect of DA on the EPSP. However, neither the D-1-rece ptor agonist SKF-38393 (1 mu M) nor the D-3-receptor agonist PD-128,90 7 (1 mu M) affected the EPSP. 5. Incubation of hippocampal slices with pertussis toxin (PTX, 5 mu g/ml) for 12 h prevented the reduction of EPSP induced by DA (0.3 mu M). 6. Rp-adenosine-3',5'-cyclic monophosph othioate (25 mu M), a potent inhibitor of protein kinase A (PKA), alon e decreased the amplitude of EPSP below baseline values and prevented the subsequent reduction by DA (0.3 mu M). 7. These results indicate t hat DA at a low concentration(less than or equal to 0.3 mu M) reduces the excitatory response of hippocampal CA1 neurons after synaptic stim ulation via the activation of presynaptic D-2 receptors. The presynapt ic action of DA is mediated by a PTX sensitive G(i)-proteins-coupled t o PKA pathway.