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Modulation of basal ganglia neurotransmission by the classical antipsychotic fluphenazine is due in part to the blockade of dopamine D1-receptors.
Coirini, H; Källström, L; Wiesel, F A; Johnson, A E.
Afiliación
  • Coirini H; Instituto de Biología y Medicina Experimental, and Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Argentina.
Brain Res Mol Brain Res ; 49(1-2): 197-210, 1997 Oct 03.
Article en En | MEDLINE | ID: mdl-9387879
Classical antipsychotics, such as fluphenazine, influence neurotransmission by blocking both dopamine D1- and D2-receptors which in turn results in widespread adaptive changes in the neurochemistry of the basal ganglia. The purpose of the present study was to determine the role of D1-receptors in mediating some of these neurochemical events, including changes in D1- and D2-receptor binding, and the expression of preproenkephalin and glutamic acid decarboxylase mRNAs. For these experiments, rats were given a depot injection of fluphenazine decanoate or injected twice daily for 21 days with the D1-receptor antagonist SCH-23390. An additional group received both fluphenazine and SCH-23390 and controls were given saline. Fluphenazine administration decreased D2-receptor binding throughout the basal ganglia while SCH-23390 was without effect. In contrast to the uniform reduction in D2-receptor binding, fluphenazine altered D1-receptor binding in a region-dependent manner. Region-dependent changes were also observed in animals given SCH-23390 which increased binding in the entopeduncular nucleus and posterior caudate-putamen without affecting other brain regions. Both fluphenazine and SCH-23390 significantly enhanced preproenkephalin and glutamic acid decarboxylase (GAD) mRNA expression in the anterior striatum. Fluphenazine also increased GAD mRNA levels in the entopeduncular nucleus. Together, these results indicate that the attenuation of D1-receptor-mediated neurotransmission modulates a number of clinically relevant neurochemical processes in the basal ganglia.
Asunto(s)
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ganglios Basales / Receptores de Dopamina D2 / Receptores de Dopamina D1 / Transmisión Sináptica / Flufenazina Límite: Animals Idioma: En Revista: Brain Res Mol Brain Res Asunto de la revista: BIOLOGIA MOLECULAR / CEREBRO Año: 1997 Tipo del documento: Article País de afiliación: Argentina Pais de publicación: Países Bajos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ganglios Basales / Receptores de Dopamina D2 / Receptores de Dopamina D1 / Transmisión Sináptica / Flufenazina Límite: Animals Idioma: En Revista: Brain Res Mol Brain Res Asunto de la revista: BIOLOGIA MOLECULAR / CEREBRO Año: 1997 Tipo del documento: Article País de afiliación: Argentina Pais de publicación: Países Bajos