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 microM) potentiated N-methyl-d-aspartate (NMDA; 10mM)-evoked depolarizations, but did not change those elicited by alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid (AMPA; 1mM). Dopamine (100 microM) increased the amplitude of the NMDA (30 microM)-induced currents as well, and 1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393; 1, 10 microM), 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 microM), a D(1) receptor antagonist, reversed both the dopamine- and the SKF 38393-evoked potentiation. The D(2) receptor agonists lisuride and quinpirole (10 microM both), as well as noradrenaline (100 microM) failed to mimic the stimulatory effect of dopamine. Isoproterenol (1, 10 microM) concentration-dependently facilitated NMDA responses. However, neither this effect at 10 microM nor that of dopamine at 100 microM could be antagonized by propranolol (10 microM), a non-selective beta adrenoceptor blocker. The isoproterenol-induced facilitation of NMDA currents was abolished by SCH 23390 (10 microM). 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.
Wirkner
Kerstin
K
Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, Härtelstrasse 16-18, D-04107 Leipzig, Germany. kerstin.wirkner@medizin.uni-leipzig.de
Krause
Thomas
T
Köles
Laszlo
L
Thümmler
Susanne
S
Al-Khrasani
Mahmoud
M
Illes
Peter
P
D000818:Animals; D004298:Dopamine / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004357:Drug Synergism; D066298:In Vitro Techniques; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011941:Receptors, Adrenergic / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000502:physiology*
D065127:Dopamine D2 Receptor Antagonists; D011941:Receptors, Adrenergic; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016202:N-Methylaspartate; D004298:Dopamine