Effect of Subchronic Intravenous Morphine Infusion and Naloxone-Precipitated Morphine Withdrawal on P-gp and Bcrp at the Rat Blood-Brain Barrier

• Tipo: Artigo em Revista Científica Internacional
• Data: 2016

Autores

Chaves, C (Autor) Outra; Gomez Zepeda, D (Autor) Outra; Auvity, S (Autor) Outra; Menet, MC (Autor) Outra; Crete, D (Autor) Outra; Labat, L (Autor) Outra; Fernando Remiao (Autor) FFUP; Cisternino, S (Autor) Outra; Decleves, X (Autor) Outra

Revista

Título: Journal of Pharmaceutical Sciences

Vol. 105

Páginas: 350-358

ISSN: 0022-3549

Editora: Elsevier

Indexação

ISI Web of Knowledge - 5 Citações

Scopus - 9 Citações

Outras Informações

ID Authenticus: P-00K-EGR

DOI: 10.1002/jps.24697

Abstract (EN): Chronic morphine regimen increases P-glycoprotein (P-gp) and breast cancer-resistance protein (Bcrp) expressions at the rat blood-brain barrier (BBB) but what drives this effect is poorly understood. The objective of this study is to assess subchronic continuous morphine infusion and naloxone-precipitated morphine withdrawal effects on P-gp/Bcrp contents and activities at the rat BBB. Rats were treated either with (i) a continuous i.v. morphine for 120 h, (ii) escalating morphine dosing (10-40 mg/kg, i.p., 5 days), (iii) a chronic morphine regimen (10 mg/kg s.c., 5 days) followed by a withdrawal period (2 days) and treatment for 3 additional days. Animal behavior was assessed after naloxone-precipitated withdrawal (1 mg/kg, s.c.). P-gp/Bcrp expressions and activities were determined in brain microvessels by qRT-PCR, Western blot, UHPLC-MS/MS, and in situ brain perfusion of P-gp or Bcrp substrates. Results show continuous i.v. morphine did not change P-gp/Bcrp protein levels in rat brain microvessels, whereas naloxone-precipitated withdrawal after escalating or chronic morphine dose regimen increased Mdr1a and Bcrp mRNA levels by 1.4-fold and 2.4-fold, respectively. Conversely, P-gp/Bcrp protein expressions remained unchanged after naloxone administration, and brain uptake of [H-3]-verapamil (P-gp) and [H-3]mitoxantrone (Bcrp) was not altered. The study concludes subchronic morphine infusion and naloxone-precipitated morphine withdrawal have poor effect on P-gp/Bcrp levels at the rat BBB.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 9