[Abstract Title]. - Society for Neuroscience

Program#/Poster#: 255.9/Y24
Topic: C.15.h. Affective disorders: Animal models
Title: Acute stress responsiveness of the neurotrophin BDNF in rat hippocampus is modulated
by chronic antidepressant treatment
Authors: *M. A. RIVA 1 , F. CALABRESE 1 , A. CATTANEO 2 , M. MANCINI 3 , M.
GENNARELLI 2 , G. RACAGNI 1 , R. MOLTENI 1 ;
1 Dept Pharmacol Sci., Univ. Milan, Milan, Italy; 2 IRCCS Fatebenefratelli San Giovanni di Dio,
Brescia, Italy; 3 Eli Lilly Italia S.p.A., Sesto Fiorentino (FI), Italy
Abstract: Compelling evidence suggests that mood disorders are characterized by reduced
neuronal plasticity that might ultimately be normalized by pharmacological intervention.
However, the potential of psychotropic drugs to improve neuronal plasticity can also be due to
the modulation of specific proteins and systems under a challenging condition. On this basis, our
study aimed to establish whether chronic antidepressant treatment could alter the modulation of
the neurotrophin brain-derived neurotrophic factor (BDNF) under a stressful condition.
In order to do so, adult male Sprague-Dawley rats were treated for 21 days with vehicle or with
the SNRI duloxetine (DLX, 10 mg/kg). Twenty-four hours after the last injection, half of the
animals were exposed to an acute swim stress (5 min) and were killed 15 min later. We found
that, although minor changes on hippocampal BDNF mRNA levels were observed under resting
conditions, chronic DLX treatment was able to affect rapid transcriptional changes produced by
the acute swim stress. Indeed while the mRNA levels of BDNF exon IV were up-regulated by
stress in vehicle as well as in DLX-treated rats, a significant increase of exon VI was only found
in rats that were pretreated with the antidepressant. These differential effects are in part due to
selective changes in stress-induced activation of signalling pathways involved in the control of
BDNF transcription. Moreover, we found that chronic duloxetine treatment can also modulate
the intracellular trafficking of BDNF protein following the acute stress. In fact the levels of
mBDNF in the synaptosomal compartment were significantly increased following stress in DLXtreated
rats, but not in control animals. Conversely the levels of mBDNF in the whole
homogenate were not affected by stress exposure.
In summary, our results consolidate the idea that an up-regulation of the neurotrophin BDNF
may represent a common event of antidepressant treatment. Moreover, we provide evidence for a
novel degree of modulation of synaptic plasticity, which refers to the possibility that
antidepressant drugs might alter rapid transcriptional changes of neurotrophin exons and can also
enhance the synaptic pool of the neurotrophin under challenging conditions.
Disclosures: M.A. Riva , None; F. Calabrese, None; A. Cattaneo, None; M. Mancini, Eli
Lilly Italia S.p.A., Sesto Fiorentino, Italy, A. Employment (full or part-time); M. Gennarelli,
None; G. Racagni, None; R. Molteni, None.
Poster