Sub-chronic exposure to atomoxetine up-regulates BDNF expression and signalling in the brain of adolescent spontaneously hypertensive rats: Comparison with methylphenidate

被引：55

作者：

Fumagalli, Fabio ^{[1
,2
]}

Cattaneo, Annamaria ^{[3
]}

Caffino, Lucia ^{[1
]}

Ibba, Marcello ^{[4
]}

Racagni, Giorgio ^{[1
,2
,5
]}

Carboni, Ezio ^{[4
]}

Gennarelli, Massimo ^{[3
,6
]}

Riva, Marco Andrea ^{[1
,2
]}

机构：

[1] Univ Milan, Dept Pharmacol Sci, Ctr Neuropharmacol, I-20133 Milan, Italy

[2] Ctr Excellence Neurodegenerat Dis, I-20133 Milan, Italy

[3] IRCCS San Giovanni di Dio Fatebenefratelli, Genet Unit, Brescia, Italy

[4] Univ Cagliari, Dept Toxicol, Cagliari, Italy

[5] IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy

[6] Univ Brescia, Sch Med, Dept Biomed Sci & Biotechnol, Biol & Genet Div, Brescia, Italy

来源：

PHARMACOLOGICAL RESEARCH | 2010年 / 62卷 / 06期

关键词：

Attention-Deficit/Hyperactivity Disorder; Brain derived neurotrophic factor; Methylphenidate; Atomoxetine; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; NEUROTROPHIC FACTOR EXPRESSION; FACTOR GENE-EXPRESSION; PREFRONTAL CORTEX; PERIADOLESCENT RATS; EXTRACELLULAR LEVELS; ADULT RATS; DOPAMINE; STRESS; ADHD;

D O I：

10.1016/j.phrs.2010.07.009

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The stimulant methylphenidate and the non-stimulant atomoxetine are widely used for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) but the molecular mechanisms of their therapeutic action are not fully understood The aim of our study was to investigate in adolescent rats the subchronic effect of these two drugs on neuronal plasticity through a detailed analysis of BDNF expression and signalling in order to establish the contribution of these mechanisms in the pharmacotherapy of ADHD Atomoxetine (ATX) up-regulated BDNF mRNA levels in the hippocampus whereas methylphenidate (MPH) Increased BDNF gene expression in the nucleus accumbens and caudate-putamen Opposite effects were seen in the prefrontal cortex a critical region in attention disorders where ATX increased while MPH reduced total and exon IV BDNF mRNA levels Analysis of BDNF-mediated signalling in the prefrontal cortex revealed that ATX enhanced AKT and GSK3 beta phosphorylation whereas MPH reduced the synaptic levels of trkB the high-affinity BDNF receptor and ERK1/2 activation Our findings show that ATX and MPH exert an opposite modulation of the BDNF system primarily in prefrontal cortex that independently from the behavioral control exerted by the two drugs may be Important for long-term consequences on cognitive function (C) 2010 Elsevier Ltd All rights reserved

引用

页码：523 / 529

页数：7

共 56 条

[41] Deficiency in the Inhibitory Serine-Phosphorylation of Glycogen Synthase Kinase-3 Increases Sensitivity to Mood Disturbances [J].