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The impact of dopamine D2-like agonist/antagonist on [18F]VAT PET measurement of VAChT in the brain of nonhuman primates.
Liu, Hui; Luo, Zonghua; Gu, Jiwei; Su, Yi; Flores, Hubert; Parsons, Stanley M; Zhou, Yun; Perlmutter, Joel S; Tu, Zhude.
Afiliación
  • Liu H; Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Luo Z; Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Gu J; Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Su Y; Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Flores H; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Parsons SM; Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA.
  • Zhou Y; Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Perlmutter JS; Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Neuroscience, Physical Therapy and Occupational Therapy, Washington University School of Medicine, S
  • Tu Z; Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: tuz@mir.wustl.edu.
Eur J Pharm Sci ; 143: 105152, 2020 Feb 15.
Article en En | MEDLINE | ID: mdl-31740395
Vesicular acetylcholine transporter (VAChT) is a promising target for a PET measure of cholinergic deficits which contribute to cognitive impairments. Dopamine D2-like agonists and antagonists are frequently used in the elderly and could alter cholinergic function and VAChT level. Therefore, pretreatment with dopamine D2-like drugs may interfere with PET measures using [18F]VAT, a specific VAChT radioligand. Herein, we investigated the impact of dopaminergic D2-like antagonist/agonist on VAChT level in the brain of macaques using [18F]VAT PET. PET imaging studies were carried out on macaques at baseline or pretreatment conditions. For pretreatment, animals were injected using a VAChT inhibitor (-)-vesamicol, a D2-like antagonist (-)-eticlopride, and a D2-like agonist (-)-quinpirole, separately. (-)-Vesamicol was injected at escalating doses of 0.025, 0.05, 0.125, 0.25 and 0.35 mg/kg; (-)-eticlopride was injected at escalating doses of 0.01, 0.10 and 0.30 mg/kg; (-)-quinpirole was injected at escalating doses of 0.20, 0.30, and 0.50 mg/kg. PET data showed [18F]VAT uptake declined in a dose-dependent manner by (-)-vesamicol pretreatment, demonstrating [18F]VAT uptake is sensitive to reflect the availability of VAChT binding sites. Furthermore, (-)-eticlopride increased [18F]VAT striatal uptake in a dose-dependent manner, while (-)-quinpirole decreased its uptake, suggesting striatal VAChT levels can be regulated by D2-like drug administration. Our findings confirmed [18F]VAT offers a reliable tool to in vivo assess the availability of VAChT binding sites. More importantly, PET with [18F]VAT successfully quantified the impact of dopaminergic D2-like drugs on striatal VAChT level, suggesting [18F]VAT has great potential for investigating the interaction between dopaminergic and cholinergic systems in vivo.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Receptores de Dopamina D2 / Agonistas de Dopamina / Tomografía de Emisión de Positrones / Proteínas de Transporte Vesicular de Acetilcolina / Antagonistas de los Receptores de Dopamina D2 Límite: Animals Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Encéfalo / Receptores de Dopamina D2 / Agonistas de Dopamina / Tomografía de Emisión de Positrones / Proteínas de Transporte Vesicular de Acetilcolina / Antagonistas de los Receptores de Dopamina D2 Límite: Animals Idioma: En Revista: Eur J Pharm Sci Asunto de la revista: FARMACIA / FARMACOLOGIA / QUIMICA Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos