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Hokkaido University Collection of Scholarly and Academic Papers >
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Serotonin 5-HT2C receptor knockout in mice attenuates fear responses in contextual or cued but not compound context-cue fear conditioning
| Title: | Serotonin 5-HT2C receptor knockout in mice attenuates fear responses in contextual or cued but not compound context-cue fear conditioning |
| Authors: | Bouchekioua, Youcef Browse this author | | Nebuka, Mao Browse this author | | Sasamori, Hitomi Browse this author | | Nishitani, Naoya Browse this author | | Sugiura, Chiaki Browse this author | | Sato, Masaaki Browse this author →KAKEN DB | | Yoshioka, Mitsuhiro Browse this author →KAKEN DB | | Ohmura, Yu Browse this author →KAKEN DB |
| Issue Date: | 11-Feb-2022 |
| Publisher: | Springer Nature |
| Journal Title: | Translational Psychiatry |
| Volume: | 12 |
| Issue: | 1 |
| Start Page: | 58 |
| Publisher DOI: | 10.1038/s41398-022-01815-2 |
| Abstract: | Previous findings have proposed that drugs targeting 5-HT2C receptors could be promising candidates in the treatment of trauma- and stress-related disorders. However, the reduction of conditioned freezing observed in 5-HT2C receptor knock-out (KO) mice in previous studies could alternatively be accounted for by increased locomotor activity. To neutralize the confound of individual differences in locomotor activity, we measured a ratio of fear responses during versus before the presentation of a conditioned stimulus previously paired with a footshock (as a fear measure) by utilizing a conditioned licking suppression paradigm. We first confirmed that 5-HT2C receptor gene KO attenuated fear responses to distinct types of single conditioned stimuli (context or tone) independently of locomotor activity. We then assessed the effects of 5-HT2C receptor gene KO on compound fear responses by examining mice that were jointly conditioned to a context and a tone and later re-exposed separately to each. We found that separate re-exposure to individual components of a complex fear memory (i.e., context and tone) failed to elicit contextual fear extinction in both 5-HT2C receptor gene KO and wild-type mice, and also abolished differences between genotypes in tone-cued fear extinction. This study delineates a previously overlooked role of 5-HT2C receptors in conditioned fear responses, and invites caution in the future assessment of molecular targets and candidate therapies for the treatment of PTSD. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/85261 |
| 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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