Dopamine Modulation of Synaptic Transmission in Rat Prefrontal Cortex: an in Vitro Electrophysiological Study

The prefrontal cortex is innervated by a well-defined dopaminergic bundle originating from the brainstem and is a key structure in higher order mental processes. We have studied the effects of dopamine (DA) on layer V pyramidal cells of the prefrontal cortex using intracellular recording in rat brain slices maintained in vitro. Bath administration of DA (50-100 microM) had weak effects on membrane properties of these neurons. In contrast, DA markedly decreased all components of the synaptic responses evoked by electrical stimulation of layer I or VI, and in particular the monosynaptic excitatory postsynaptic potential (EPSP) which arises from activation of glutamatergic receptors. The afferents from layer VI seemed less affected by DA than those from layer I. The NMDA (N-methyl-D-aspartate) and AMPA (alpha-amino-3-hydroxy-5-methyl-isoxazolepropionic acid) components of monosynaptic EPSPs were equally reduced by DA. The isolated fast gabaergic potential (IPSP) resulting from GABAA receptors activation was similarly reduced by DA. The suppressive effect of DA on glutamatergic transmission was partially mimicked by the D1 receptor agonist SKF 38393 (50 microM) whereas the D2 receptor agonist quinpirole (50 microM) was ineffective. Conversely, this effect was antagonized by the D1 receptor blocker SCH 23390 (100 microM) but not by the D2 receptor antagonist sulpiride (100 microM). These findings indicate that DA decreases both glutamatergic and gabaergic synaptic transmission in neurons located in layer V of rat prefrontal cortex. These results also suggest that D1 dopamine receptor is involved in the decrement of glutamatergic transmission. These interactions between DA and glutamate are important in regard to the suspected implications of both neurotransmitters in psychiatric diseases.