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Noradrenaline reuptake inhibition increases control of impulsive action by activating D1-like receptors in the infralimbic cortex
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| Title: | Noradrenaline reuptake inhibition increases control of impulsive action by activating D1-like receptors in the infralimbic cortex |
| Authors: | Sasamori, Hitomi 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: | Impulsivity | | Impulsive behavior | | Behavioral inhibition | | SNRI | | Microdialysis | | Dopamine |
| Issue Date: | 5-Feb-2019 |
| Publisher: | Elsevier |
| Journal Title: | European journal of pharmacology |
| Volume: | 844 |
| Start Page: | 17 |
| End Page: | 25 |
| Publisher DOI: | 10.1016/j.ejphar.2018.11.041 |
| Abstract: | Higher impulsivity is a risk factor for criminal involvement, substance abuse, and suicide. However, only a few drugs are clinically available for the treatment of deficient impulse control. We recently proposed a strategy for identifying potential drugs to treat such disorders by investigating clinically available drugs that increase extracellular dopamine levels in the medial prefrontal cortex and stimulate dopamine D1-like receptors without increasing extracellular dopamine levels in the ventral striatum. To determine whether this strategy is promising, we examined the effects of duloxetine, a serotonin-noradrenaline reuptake inhibitor that might meet these criteria, on impulsive action in adult male Wistar/ST rats using a 3-choice serial reaction time task. The effects of duloxetine on extracellular dopamine levels in the medial prefrontal cortex and nucleus accumbens, a part of the ventral striatum were evaluated using in vivo microdialysis, as the noradrenaline transporter transports dopamine in some brain regions. Our results showed that the administration of duloxetine reduced impulsive actions and increased extracellular dopamine levels in the mPFC but not in the nucleus accumbens. Microinjection of a selective D1-like receptor antagonist into the infralimbic cortex blocked the suppression of impulsive action by duloxetine. In addition, we demonstrated that the microinjection also blocked the suppression of impulsive action by atomoxetine, a noradrenaline reuptake inhibitor and an established anti-impulsive drug. These results support our proposed strategy for identifying and developing anti-impulsivity drugs. |
| Rights: | © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ | | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/76693 |
| 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)
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Submitter: 大村 優
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