Serotonin 5-HT2C receptor knockout in mice attenuates fear responses in contextual or cued but not compound context-cue fear conditioning.
Transl Psychiatry
; 12(1): 58, 2022 02 11.
Article
en En
| MEDLINE
| ID: mdl-35145065
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Señales (Psicología)
/
Receptor de Serotonina 5-HT2C
/
Miedo
Límite:
Animals
Idioma:
En
Revista:
Transl Psychiatry
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA