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

Fabio Fumagalli, Annamaria Cattaneo, Lucia Caffino, Marcello Ibba, Giorgio Racagni, Ezio Carboni, Massimo Gennarelli, Marco Andrea Riva

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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 sub-chronic 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 GSK3β 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.

Original languageEnglish
Pages (from-to)523-529
Number of pages7
JournalPharmacological Research
Volume62
Issue number6
DOIs
Publication statusPublished - Dec 2010

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Methylphenidate
Brain-Derived Neurotrophic Factor
Inbred SHR Rats
Up-Regulation
Brain
Prefrontal Cortex
Attention Deficit Disorder with Hyperactivity
trkB Receptor
Messenger RNA
Neuronal Plasticity
Putamen
Nucleus Accumbens
Pharmaceutical Preparations
Cognition
Atomoxetine Hydrochloride
Exons
Hippocampus
Phosphorylation
Gene Expression
Drug Therapy

Keywords

  • Atomoxetine
  • Attention-Deficit/Hyperactivity Disorder
  • Brain derived neurotrophic factor
  • Methylphenidate

ASJC Scopus subject areas

  • Pharmacology

Cite this

Sub-chronic exposure to atomoxetine up-regulates BDNF expression and signalling in the brain of adolescent spontaneously hypertensive rats : Comparison with methylphenidate. / Fumagalli, Fabio; Cattaneo, Annamaria; Caffino, Lucia; Ibba, Marcello; Racagni, Giorgio; Carboni, Ezio; Gennarelli, Massimo; Riva, Marco Andrea.

In: Pharmacological Research, Vol. 62, No. 6, 12.2010, p. 523-529.

Research output: Contribution to journalArticle

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