title: Modulatory actions of dopamine on NMDA receptor-mediated responses are reduced in D1A-deficient mutant mice.
abstract: The role of D1 dopamine (DA) receptors in mediating the ability of DA to modulate responses attributable to activation of NMDA receptors was examined in mice lacking D1A dopamine receptors. Specifically, experiments were designed to test the hypothesis that the ability of DA to potentiate responses mediated by activation of NMDA receptors was attributable to activation of D1 receptors. Based on this hypothesis, we would predict that in the D1A mutant mouse, either DA would not induce enhancement of NMDA-mediated responses, or the enhancement would be severely attenuated. The results provided evidence to support the hypothesis. In mutant mice, DA and D1 receptor agonists did not potentiate responses mediated by activation of NMDA receptors. In contrast, in control mice, both DA and D1 receptor agonists markedly potentiated responses mediated by activation of NMDA receptors. The effects of DA in attenuating responses mediated by activation of non-NMDA receptors also were altered in the mutant, suggesting that this action of DA may require coupling or interactions between D1 and D2 receptors. The present studies also provided an opportunity to assess some of the basic electrophysiological and morphological properties of neostriatal neurons in mice lacking D1A DA receptors. Resting membrane potential, action potential parameters, input resistance, excitability, somatic size, dendritic extent, and estimates of spine density in mutants and controls were similar, suggesting that these basic neurophysiological and structural properties have not been changed by the loss of the D1A DA receptor.
authors.affiliation: Mental Retardation Research Center, University of California, Los Angeles 90024-1759, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Levine
authors.forename: K L
authors.initials: KL
authors.lastname: Altemus
authors.forename: C
authors.initials: C
authors.lastname: Cepeda
authors.forename: H C
authors.initials: HC
authors.lastname: Cromwell
authors.forename: C
authors.initials: C
authors.lastname: Crawford
authors.forename: M A
authors.initials: MA
authors.lastname: Ariano
authors.forename: J
authors.initials: J
authors.lastname: Drago
authors.forename: D R
authors.initials: DR
authors.lastname: Sibley
authors.forename: H
authors.initials: H
authors.lastname: Westphal
mesh_terms: D000818:Animals; D001483:Base Sequence; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004594:Electrophysiology; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
chemical_list: D018491:Dopamine Agonists; D015335:Molecular Probes; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D016194:Receptors, N-Methyl-D-Aspartate; D004298:Dopamine