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Title	en Milnacipran affects mouse impulsive, aggressive, and depressive-like behaviors in a distinct dose-dependent manner
Creator	en Tsutsui-Kimura, Iku en Ohmura, Yu NRID 1000080597659 en Yoshida, Takayuki NRID 1000060374229 en Yoshioka, Mitsuhiro NRID 1000040182729
Accessrights	open access
Rights	http://creativecommons.org/licenses/by-nc-nd/4.0/ en Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
Subject	Other en Serotonin/norepinephrine reuptake inhibitor Other en Response inhibition Other en Violence Other en Helplessness Other en Depression NDC 490
Description	Abstract en 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.
Publisher	en Elsevier
Date	Issued2017-07
Language	eng
Resource Type	journal article
Version Type	VoR
Identifier	HDL http://hdl.handle.net/2115/67315
Relation	isIdenticalTo DOI https://doi.org/10.1016/j.jphs.2017.06.004 PMID 28694090
Journal	PISSN 1347-8613 en Journal of pharmacological sciences Volume Number134 Issue Number3 Page Start181 Page End189
File	fulltext 1-s2.0-S1347861317300907-main.pdf 1.58 MB (application/pdf) Issued2017-07 fulltext 1-s2.0-S1347861317300907-mmc1.docx 188.37 KB (application/vnd.openxmlformats-officedocument.wordprocessingml.document) Issued2017-07 fulltext 1-s2.0-S1347861317300907-mmc2.docx 17.05 KB (application/vnd.openxmlformats-officedocument.wordprocessingml.document) Issued2017-07
Oaidate	2023-07-26