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Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner

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Title: Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner
Authors: Tsutsui-Kimura, Iku Browse this author
Ohmura, Yu Browse this author →KAKEN DB
Yoshida, Takayuki Browse this author →KAKEN DB
Yoshioka, Mitsuhiro Browse this author →KAKEN DB
Keywords: Serotonin/norepinephrine reuptake inhibitor
Response inhibition
Issue Date: Jul-2017
Publisher: Elsevier
Journal Title: Journal of pharmacological sciences
Volume: 134
Issue: 3
Start Page: 181
End Page: 189
Publisher DOI: 10.1016/j.jphs.2017.06.004
PMID: 28694090
Abstract: Serotonin/noradrenaline reuptake inhibitors (SNRIs) are widely used for the treatment for major depressive disorder, but these drugs induce several side effects including increased aggression and impulsivity, which are risk factors for substance abuse, criminal involvement, and suicide. To address this issue, milnacipran (0, 3, 10, or 30 mg/kg), an SNRI and antidepressant, was intraperitoneally administered to mice prior to the 3-choice serial reaction time task, residente-intruder test, and forced swimming test to measure impulsive, aggressive, and depressive-like behaviors, respectively. A milnacipran dose of 10 mg/kg suppressed all behaviors, which was accompanied by increased dopamine and serotonin levels in the medial prefrontal cortex (mPFC) but not in the nucleus accumbens (NAc). Although the most effective dose for depressive-like behavior was 30 mg/kg, the highest dose increased aggressive behavior and unaffected impulsive behavior. Increased dopamine levels in the NAc could be responsible for the effects. In addition, the mice basal impulsivity was negatively correlated with the latency to the first agonistic behavior. Thus, the optimal dose range of milnacipran is narrower than previously thought. Finding drugs that increase serotonin and dopamine levels in the mPFC without affecting dopamine levels in the NAc is a potential strategy for developing novel antidepressants.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 大村 優

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