BDNF level in the rat prefrontal cortex increases following chronic but not acute treatment with duloxetine, a dual acting inhibitor of noradrenaline and serotonin re-uptake.
OBJECTIVE
Brain-Derived Neurotrophic Factor (BDNF) has a central role in neuronal survival, differentiation, and plasticity. The brain level of BDNF is changed by several mood stabilizers and antidepressant drugs acting on neurotransmitters such as noradrenaline and serotonin. We investigated the effects of acute and chronic treatment with Duloxetine, a new drug blocking the re-uptake of serotonin and noradrenaline (SNRI), on BDNF level in the prefrontal cortex, cerebrospinal fluid, plasma, and serum.


METHODS
Wistar male rats were treated with acute (single treatment) and chronic oral administration (14 days) of different concentrations of Duloxetine (10, 30, and 100 mg/kg/day). At the end of the treatment periods, samples of blood, CSF and the prefrontal cortex were collected. BDNF levels were measured by ELISA. Levels of mature and precursor form of BDNF were measured by Western blot analysis.


RESULTS
Animals treated with the Duloxetine at all concentrations and examined after 1 and 24 h (single treatment) did not reveal a significant change in the total BDNF level. In animals treated for 14 days with Duloxetine at 30 and 100 mg/kg, the total BDNF level increased significantly in the prefrontal cortex and CSF, but not in the plasma and serum. Using a specific antibody and Western blot we showed that the mature, but not the precursor, form of BDNF was significantly increased in the prefrontal cortex of rats treated for 14 days with Duloxetine at 30 mg/kg/day.


CONCLUSIONS
Our results show a major finding that repeated, but not single, Duloxetine treatment increases the level of BDNF in the prefrontal cortex.
Mannari
Claudio
C
Department of Neuroscience, Sect. Pharmacology, University of Pisa, Pisa, Italy.
Origlia
Nicola
N
Scatena
Alessia
A
Del Debbio
Alessandro
A
Catena
Mario
M
Dell'agnello
Grazia
G
Barraco
Alessandra
A
Giovannini
Luca
L
Dell'osso
Liliana
L
Domenici
Luciano
L
Piccinni
Armando
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000068736:Duloxetine Hydrochloride; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*; D013997:Time Factors
D019208:Brain-Derived Neurotrophic Factor; D000068736:Duloxetine Hydrochloride; D009638:Norepinephrine; D020033:Protein Isoforms; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D013876:Thiophenes