Abstract
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.
Highlights
The nucleus accumbens, which forms the ventral part of the striatum, has been proposed to serve as an interface between limbic and motor systems [1]
In an effort to clarify how the NMDA and AMPA/KA excitatory postsynaptic currents (EPSCs) might be affected in the nucleus accumbens (nAcb) by dopaminergic innervation, we investigated the effect of DA on NMDA and AMPA/KA excitatory synaptic transmission in this region
To validate our experimental assumption that the effects of DA on compound EPSCs effectively represented the effects on AMPA/KA and NMDA receptor-mediated EPSCs, we studied the effects of DA on pharmacologically isolated AMPA/KA and NMDA mediated EPSC using APV (50:M) and CNQX (20:M), respectively
Summary
The nucleus accumbens (nAcb), which forms the ventral part of the striatum, has been proposed to serve as an interface between limbic and motor systems [1]. Glutamatergic and dopaminergic afferents have been found to converge on the same dendritic spines of medium spiny (MS) GABAergic projecting neurons in the nAcb [6],[7,8],[9],[10]. This closed spatial relationship suggests a possible interaction between the glutamatergic and dopaminergic systems at the pre- and/or postsynaptic levels. Recent finding of D1/NMDA receptor complexes in striatal and hippocampal tissue indicates possible direct protein-protein interactions between D1 and NMDA receptors [13]
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