Dopamine depresses excitatory synaptic transmission onto rat subicular neurons via presynaptic D1-like dopamine receptors

Schizophrenia is considered to be associated with an abnormal functioning o f the hippocampal output. The high clinical potency of antipsychotics that act as antagonists at dopamine (DA) receptors indicate a hyperfunction of t he dopaminergic system. The subiculum obtains information from area CA1 and the entorhinal cortex and represents the major output region of the hippoc ampal complex. To clarify whether an enhanced dopaminergic activity alters the hippocampal output, the effect of DA on alveus- and perforant path-evok ed excitatory postsynaptic currents (EPSCs) in subicular neurons was examin ed using conventional intracellular and whole cell voltage-clamp recordings . Dopamine (100 mu M) depressed alveus- elicited (S)-alpha-amino-3-hydroxy- 5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated EPSCs to 56 +/- 8% of control while perforant path-evoked EPSCs were attenuated to only 76 +/- 7% of control. Dopamine had no effect on the EPSC kinetics. Dopamine r educed the frequency of spontaneous miniature EPSCs without affecting their amplitudes. The sensitivity of subicular neurons to the glutamate receptor agonist (S)-alpha-amino-3-hydoxy-5-methyl-4-isoxazolepropionic acid was un changed by DA pretreatment, excluding a postsynaptic mechanism for the obse rved reduction of excitatory synaptic transmission. The effect of DA on evo ked EPSCs was mimicked by the D1 receptor agonist SFK 38393 and partially a ntagonized by the D1 receptor antagonist SCH 23390. While the D2 receptor a gonist quinelorane failed to reduce the EPSCs, the D2 receptor antagonist s ulpiride did not block the action of DA. The results indicate that DA stron gly depresses the hippocampal and the entorhinal excitatory input onto subi cular neurons by decreasing the glutamate release following activation of p resynaptic D1-like DA receptors.