Chronic treatment with fluoxetine up-regulates cellular BDNF mRNA expression in rat dopaminergic regions
During the last few years several studies have highlighted the possibility that major depression can be characterized by a general reduction in brain plasticity and an increased vulnerability under challenging situations. Such dysfunction may be the consequence of reduced expression and function of proteins important for neuroplasticity such as brain-derived neurotrophic factor (BDNF). On this basis, by using a sensitive non-radioactive in-situ hybridization, we evaluated the effects of a chronic treatment with fluoxetine on BDNF expression within rat dopaminergic regions. In fact, besides the well-established role of the hippocampus, increasing evidence indicates that other brain regions may be involved in the pathophysiology of depression and consequently be relevant for the therapeutic action of antidepressant drugs. Our results indicate that 3 wk of fluoxetine administration up-regulates BDNF mRNA levels selectively within structures belonging to the meso-cortico-limbic pathway. The expression of the neurotrophin is significantly increased in the ventral tegmental area, prefrontal cortex, and shell region of the nucleus accumbens, whereas no changes were detected in the substantia nigra and striatum. Moreover, in agreement with previous studies, fluoxetine increased BDNF mRNA levels in the hippocampus, an effect that was limited to the cell bodies without any change in its dendritic targeting. These data show that chronic treatment with fluoxetine increases BDNF gene expression not only in limbic areas but also in dopaminergic regions, suggesting that such an effect may contribute to improve the function of the dopaminergic system in depressed subjects.(Received January 3 2005)
(Reviewed February 24 2005)
(Revised May 2 2005)
(Accepted May 5 2005)
(Published Online July 22 2005)
Key Words: Antidepressants; dopaminergic system; gene expression; in-situ hybridization; neurotrophin.
c1 Center of Neuropharmacology, Department of Pharmacological Sciences, Via Balzaretti, 9, 20133 Milan, Italy. Tel.: +39-0250318334 Fax: +39-0250318278 E-mail: M.Riva@unimi.it