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Brain Region-Specific Effects of Short-Term Treatment with Duloxetine, Venlafaxine, Milnacipran and Sertraline on Monoamine Metabolism in Rats

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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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Authors and Affiliations

  1. Department of Anatomy I, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-Ku, Tokyo, 142-8555, Japan

    Katsumasa Muneoka & Seiji Shioda

  2. Department of Neuropsychiatry, Kagoshima University Faculty of Medicine, Kagoshima, 890-8520, Japan

    Katsumasa Muneoka & Morikuni Takigawa

  3. Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, 260-8677, Japan

    Yukihiko Shirayama

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  1. Katsumasa Muneoka
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  2. Yukihiko Shirayama
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  3. Morikuni Takigawa
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  4. Seiji Shioda
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Correspondence to Katsumasa Muneoka.

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Muneoka, K., Shirayama, Y., Takigawa, M. et al. Brain Region-Specific Effects of Short-Term Treatment with Duloxetine, Venlafaxine, Milnacipran and Sertraline on Monoamine Metabolism in Rats. Neurochem Res 34, 542–555 (2009). https://doi.org/10.1007/s11064-008-9818-2

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  • DOI: https://doi.org/10.1007/s11064-008-9818-2

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