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We examined brain region-specific changes in monoamines and metabolites, and their ratios, after short-term administration
of antidepressants to rats. Serotonin noradrenaline reuptake inhibitors (SNRIs; duloxetine, venlafaxine, milnacipran) and
a serotonin-selective reuptake inhibitor (SSRI; sertraline) elevated serotonin (5-HT) levels in the midbrain (MB). Duloxetine
and venlafaxine increased 5-HT levels in the brainstem and 5-HT terminal areas, whereas milnacipran and sertraline increased
levels in the brainstem only. Significant reductions in 5-HT turnover were observed in various forebrain regions, including
the hippocampus and hypothalamus, after treatment with all of the tested drugs except for milnacipran. In addition, there
was reduced 5-HT turnover in the dorsolateral frontal cortex (dlFC), the medial prefrontal cortex (mPFC), and both the dlFC
and the mPFC after treatment with duloxetine, sertraline, and venlafaxine, respectively. Venlafaxine significantly increased
dopamine (DA) levels in the nucleus accumbens (NAc) and the substantia nigra and decreased DA turnover in the NAc. Similar
changes were observed after treatment with duloxetine and sertraline in the NAc, whereas milnacipran increased DA levels in
the mPFC. Limited increases in noradrenaline levels were detected after treatment with duloxetine, venlafaxine, or sertraline,
but not after treatment with milnacipran. These results show that SNRIs and SSRIs induced region-specific monoaminergic changes
after short-term treatment. 相似文献
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Mannari C Origlia N Scatena A Del Debbio A Catena M Dell'agnello G Barraco A Giovannini L Dell'osso L Domenici L Piccinni A 《Cellular and molecular neurobiology》2008,28(3):457-468
Aims 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.
Claudio Mannari and Nicola Origlia are contributed equally to this work. 相似文献
3.
Wakenhut F Fish PV Fray MJ Gurrell I Mills JE Stobie A Whitlock GA 《Bioorganic & medicinal chemistry letters》2008,18(15):4308-4311
The structure–activity relationship and the synthesis of novel N-benzyl-N-(pyrrolidin-3-yl)carboxamides as dual serotonin (5-HT) and noradrenaline (NA) monoamine reuptake inhibitors are described. Compounds such as 18 exhibited dual 5-HT and NA reuptake inhibition, good selectivity over dopamine (DA) reuptake inhibition and drug-like physicochemical properties consistent with CNS target space. Compound 18 was selected for further preclinical evaluation. 相似文献
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