Dopamine-glutamate interactions in the prefrontal cortex (PFC) are associated with higher order cognitive functions, and are involved in the pathophysiology of schizophrenia and addiction. Recordings with intracellular sharp microelectrodes and patch-clamp pipettes were used to investigate these interactions in layer V pyramidal cells of brain slices obtained from the rat PFC. Dopamine (100 μM) potentiated N-methyl-d-aspartate (NMDA; 10 mM)-evoked depolarizations, but did not change those elicited by α-amino-3-hydroxy-5- methyl-4-isoxazole-4-propionic acid (AMPA; 1 mM). Dopamine (100 μM) increased the amplitude of the NMDA (30 μM)-induced currents as well, and 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393; 1, 10 μM), a D 1 receptor agonist, concentration-dependently reproduced this effect. Furthermore, 7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5- tetrahydro-(1H)-3-benzapine hydrochloride (SCH 23390; 10 μM), a D 1 receptor antagonist, reversed both the dopamine- and the SKF 38393-evoked potentiation. The D 2 receptor agonists lisuride and quinpirole (10 μM both), as well as noradrenaline (100 μM) failed to mimic the stimulatory effect of dopamine. Isoproterenol (1, 10 μM) concentration- dependently facilitated NMDA responses. However, neither this effect at 10 μM nor that of dopamine at 100 μM could be antagonized by propranolol (10 μM), a non-selective β adrenoceptor blocker. The isoproterenol-induced facilitation of NMDA currents was abolished by SCH 23390 (10 μM). The results indicate that dopamine potentiates NMDA responses in layer V pyramidal cells of the PFC solely by activating D 1 receptors. D 2 receptors and α or β adrenoceptors are not involved in the dopamine-NMDA interaction.
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