title: Direct and indirect actions of dopamine on the membrane potential in medium spiny neurons of the mouse neostriatum.
abstract: Many studies have shown dopamine (DA) to have a modulatory effect on neuronal excitability, which cannot be simply classified as excitatory or inhibitory in the neostriatum. To clarify whether the responses to DA (10-30 microM) are excitatory or inhibitory in the mouse medium spiny neurons, we examined the effects of DA agonists on the synchronous potential trajectory from the resting potential to the subthreshold potential. The DA-induced potential changes, which were estimated at the subthreshold potential (approximately -60 mV), were summarized as the combination of three kinds of responses: an initial hyperpolarization lasting approximately 1 min and a slow depolarization and/or hyperpolarization lasting more than 20 min. A D(1)-like receptor agonist, R(+)-6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF81297, 1 microM) mainly induced the initial hyperpolarization and slow depolarization. A D(2)-like receptor agonist, trans-(-)-4aR-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g]quinoline hydrochloride (quinpirole, 1 microM), mainly induced the initial hyperpolarization and slow hyperpolarization. D(1)-like receptor antagonist R(+)-7-chloro-8-hydroxy-3-methyl1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390, 1 microM) depressed both the initial hyperpolarization and slow depolarization. D(2)-like receptor antagonist sulpiride (1 microM) depressed all the DA-induced responses except for the slow depolarization. TTX (0.5 microM) abolished all the DA-induced responses. Bicuculline (20 microM) and atropine (1 microM) abolished the DA-induced initial hyperpolarization and slow depolarization, respectively. Either DL-2-amino-5-phosphonopentanoic acid (AP5; 100 microM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 20 microM) blocked both the initial hyperpolarization and slow depolarization. The application of exogenous glutamate (Glu) mimicked the initial hyperpolarization and slow depolarization. These results suggest that the initial hyperpolarization is mainly due to GABA release via the cooperative action of D(1)- and D(2)-like receptors and Glu receptors in GABAergic interneurons, whereas the slow depolarization is mediated by acetylcholine (ACh) release via the cooperative action of mainly D(1)-like receptors and Glu receptors in cholinergic interneurons. The potential oscillation was generated at the subthreshold level in a Ba(2+)-, AP5-, CNQX-, bicuculline-, and atropine-containing medium. The oscillation depressed after the addition of TTX, Co(2+), or DA. In DA agonists, quinpirole rather than SKF81297 had a more depressive effect on the potential oscillation. These results indicate that the slow hyperpolarization is due to the suppression of noninactivating Na(+)-Ca(2+) conductances via mainly D(2)-like receptors in the medium spiny neurons. In conclusion, the DA actions on the medium spiny neurons show a transient inhibition by the activation of D(1)- and D(2)-like receptors in mainly GABAergic interneurons and a tonic excitation and/or inhibition by the activation of mainly D(1)-like receptors in cholinergic interneurons and by the activation of mainly D(2)-like receptors in the medium spiny neurons, respectively.
authors.affiliation: Department of Physiology, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yasumoto
authors.forename: E
authors.initials: E
authors.lastname: Tanaka
authors.forename: G
authors.initials: G
authors.lastname: Hattori
authors.forename: H
authors.initials: H
authors.lastname: Maeda
authors.forename: H
authors.initials: H
authors.lastname: Higashi
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D017072:Neostriatum / Q000166:cytology*; D009474:Neurons / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018698:Glutamic Acid; D013779:Tetrodotoxin; C067113:SK&F 81297; D004298:Dopamine