METHYLPHENIDATE AND ATOMOXETINE AFFECT BDNF EXPRESSION IN THE BRAIN OF SPONTANEOUS HYPERTENSIVE RATS.

Caffino L;Cattaneo A;Ibba M;Sesta A;Racagni G;CARBONI, EZIO;Gennarelli M;Riva AM;Fumagalli F.

2009-01-01

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Abstract

Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder among children and adolescents characterized by impulsivity and deficit in attention and cognition. So far, the stimulant methyphenidate (MPH) is the most widely used drug although, recently, the non stimulant Atomoxetine (ATX) has been shown to produce benefit in patients. We have performed a long-term treatment with MPH and ATX on prepubertal Spontaneously Hypertensive rats (SHR), a well established animal model of the disease, starting from postnatal day 28 to 42 and sacrificing the animals 24 hours after the last drug administration. We focused our attention on the expression of the neurotrophin Brain Derived Neurotrophic Factor (BDNF) which is known to participate in cognitive processes. We found that ATX significantly increased total BDNF mRNA levels in hippocampus, frontal and prefrontal cortices of male animals whereas MPH increased the neurotrophin gene expression in nucleus accumbens only, while decreasing it in the prefrontal cortex. We then focused our attention on prefrontal cortex where ATX and MPH had an opposite effect on BDNF gene expression and we found that 1) ATX produced a specific up-regulation of exon IV mRNA levels as opposed to the reduced expression of the same exon brought about by MPH; 2) ATX, but not MPH, increased the trafficking of the neurotrophin toward the membrane in rat prefrontal cortex. Our findings point to a unique role of BDNF, and in particular of BDNF exon IV mRNA transcripts, in the action of MPH and ATX in rat prefrontal cortex which might represent a novel target for disease pharmacotherapy.