Brain Region-Specific Effects of Short-Term Treatment with Duloxetine,Venlafaxine, Milnacipran and Sertraline on Monoamine Metabolism in Rats |
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Authors: | Katsumasa Muneoka Yukihiko Shirayama Morikuni Takigawa Seiji Shioda |
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Institution: | (1) Department of Anatomy I, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo 142-8555, Japan;(2) Department of Neuropsychiatry, Kagoshima University Faculty of Medicine, Kagoshima 890-8520, Japan;(3) Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba 260-8677, Japan |
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Abstract: | 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. |
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Keywords: | Serotonin Dopamine Noradrenaline SNRI SSRI |
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