Dopamine preferentially inhibits NMDA receptor-mediated EPSCs by acting on presynaptic D1 receptors in nucleus accumbens during postnatal development.
Nucleus accumbens (nAcb), a major site of action of drugs of abuse and dopamine (DA) signalling in MSNs (medium spiny neurons), is critically involved in mediating behavioural responses of drug addiction. Most studies have evaluated the effects of DA on MSN firing properties but thus far, the effects of DA on a cellular circuit involving glutamatergic afferents to the nAcb have remained rather elusive. In this study we attempted to characterize the effects of dopamine (DA) on evoked glutamatergic excitatory postsynaptic currents (EPSCs) in nAcb medium spiny (MS) neurons in 1 to 21 day-old rat pups. The EPSCs evoked by local nAcb stimuli displayed both AMPA/KA and NMDA receptor-mediated components. The addition of DA to the superfusing medium produced a marked decrease of both components of the EPSCs that did not change during the postnatal period studied. Pharmacologically isolated AMPA/KA receptor-mediated response was inhibited on average by 40% whereas the isolated NMDA receptor-mediated EPSC was decreased by 90%. The effect of DA on evoked EPSCs were mimicked by the D1-like receptor agonist SKF 38393 and antagonized by the D1-like receptor antagonist SCH 23390 whereas D2-like receptor agonist or antagonist respectively failed to mimic or to block the action of DA. DA did not change the membrane input conductance of MS neurons or the characteristics of EPSCs produced by the local administration of glutamate in the presence of tetrodotoxin. In contrast, DA altered the paired-pulse ratio of evoked EPSCs. The present results show that the activation D1-like dopaminergic receptors modulate glutamatergic neurotransmission by preferentially inhibiting NMDA receptor-mediated EPSC through presynaptic mechanisms.
Centre de recherche Fernand-Seguin, University of Montreal, Montreal, Canada; Department of Physiology, University of Montreal, Montreal, Canada.
Liming
L
Zhang
Department of Psychiatry, University of Montreal, Montreal, Canada.
Poulomee
P
Bose
Centre de recherche Fernand-Seguin, University of Montreal, Montreal, Canada; Department of Psychiatry, University of Montreal, Montreal, Canada.
Richard A
RA
Warren
D000818:Animals; D000831:Animals, Newborn; D004298:Dopamine / Q000494:pharmacology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017661:Receptors, Presynaptic / Q000378:metabolism*
D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D017661:Receptors, Presynaptic; D004298:Dopamine