title: 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+.
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 microM) 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 microM). Furthermore, the D1/D5r-induced effect involved a sustained enhancement of both the pharmacologically isolated alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate receptor-(AMPAr-) and N-methyl-D-asparate receptor- (NMDAr-) mediated EPSCs, respectively. Such persistently enhanced AMPAr- and NMDAr-mediated 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.
authors.affiliation: Department of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, Republic of China. snyang@ndmc1.ndmctsgh.edu.tw
authors.forename: S N
authors.initials: SN
authors.lastname: Yang
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002614:Chelating Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000737:chemistry / Q000502:physiology*; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D050641:Receptors, Dopamine D5; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D001552:Benzazepines; D002614:Chelating Agents; D018491:Dopamine Agonists; C493607:Drd5 protein, rat; D018691:Excitatory Amino Acid Antagonists; D018091:Receptors, AMPA; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D050641:Receptors, Dopamine D5; D004533:Egtazic Acid; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C067113:SK&F 81297; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium