D1 but not D2 dopamine receptors or adrenoceptors mediate dopamine-induced potentiation of N-methyl-D-aspartate currents in the rat prefrontal cortex

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 muM) potentiated N-methyl-D-aspartate (NMDA; 10 mM)-evoked depolarizations, but did not change those elicited by alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA: 1 mM). Dopamine (100 muM) increased the amplitude of the NMDA (30 muM)-induced currents as well, and 1-phenyl2.3.4.5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393; 1, 10 muM), 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 muM), a D1 receptor antagonist, reversed both the dopamine- and the SKF 38393-evoked potentiation. The D-2 receptor agonists lisuride and quinpirole (10 muM both), as well as noradrenaline (100 muM) failed to mimic the stimulatory effect of dopamine. Isoproterenol (1, 10 muM) concentration-dependently facilitated NMDA responses. However, neither this effect at 10 muM nor that of dopamine at 100 muM could be antagonized by propranolol (10 muM), a non-selective beta adrenoceptor blocker. The isoproterenol-induced facilitation of NMDA currents was abolished by SCH 23390 (10 muM). 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 alpha or beta adrenoceptors are not involved in the dopamine-NMDA interaction. (C) 2004 Elsevier Ireland Ltd. All rights reserved.