Sustained enhancement of AMPA receptor- and NMDA receptor-mediated currents induced by dopamine D1/D5 receptor activation in the hippocampus: an essential role of postsynaptic Ca2+

San Nan Yang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

80 Scopus citations

Abstract

The dopaminergic system in the limbic system, particularly the D1/D5 receptor (D1/D5r), is important for certain forms of learning and memory, such as reinforcement learning, as well as the acute development of behavioral sensitization to psychostimulants such as cocaine and methamphetamine. Here, whole-cell patch-clamp recordings of evoked excitatory postsynaptic currents (EPSCs) mediated by ionotropic glutamate receptors were made from pyramidal neurons in the CA1 area of rat hippocampal slices. Activation of the D1/D5r by a selective D1/D5r agonist (±)-6-chloro-PB hydrobromide (SKF 81297; 3-100 μM) concentration-dependently induced a delayed-onset, sustained enhancement of EPSCs. The D1/D5r-induced effect was blocked by a selective D1/D5r antagonist (+)SCH 23390 hydrochloride (5 μM) Furthermore, the D1/D5r-induced effect involved a sustained enhancement of both the pharmacologically isolated α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate receptor-(AMPAr-) and N-methyl-D-asparate receptor- (NMDAr-) mediated EPSCs, respectively. Such persistently enhanced AMPAr- and NMDArmediated EPSCs were also associated with significant increases in the normalized amplitudes of the decay times of the isolated EPSCs. Blockade of NMDAr activation failed to prevent the induction of D1/D5r-induced sustained enhancement, suggesting the independence of the D1/D5r-induced effect on NMDAr activation. A rise of postsynaptic calcium was required for the induction of D1/D5r-induced sustained enhancement, being abolished by loading cells with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N '-tetracetic acid (BAPTA; 10 mM). Studies indicated that the D1/D5r activation induced a sustained enhancement of both the AMPAr- and NMDAr-mediated EPSCs in the hippocampus. Moreover, a rise in postsynaptic Ca2+ was necessary for triggering the D1/D5r-induced effect in the hippocampus, although the NMDAr-dependent mechanisms, such as the calcium entry via the NMDA channels, were not. Hippocampus (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)57-63
Number of pages7
JournalHippocampus
Volume10
Issue number1
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • AMPA receptor
  • BAPTA
  • Calcium
  • Dopamine D1/D5 receptors
  • NMDA receptor

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