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Fear generalization modulated by shock intensity and protein synthesis inhibitor.

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Title: Fear generalization modulated by shock intensity and protein synthesis inhibitor.
Authors: Dong, Xinwen (AUTHOR), Wang, Yunyun (AUTHOR), Liu, Yudan (AUTHOR), Li, Yonghui (AUTHOR)
Source: Psychopharmacology. Dec2024, Vol. 241 Issue 12, p2627-2637. 11p.
Subjects: Generalized anxiety disorder, Post-traumatic stress disorder, Stimulus generalization, Protein synthesis, White noise, Sensitization (Neuropsychology)
Abstract: Rationale: Maladaptive fear responses, including sensitized threat reactions and overgeneralization, contribute to anxiety disorders such as generalized anxiety disorder and post-traumatic stress disorder. Although stress intensity influences the generation and extent of these maladaptive fears, the underlying mechanisms remain unclear. Objectives: The present study examined whether varying footshock stress intensity and inhibition of protein synthesis have differential effect on fear sensitization and generalization in mice. Methods: Mice were subjected to a classic fear conditioning protocol involving five different levels of footshock intensities. Prior to fear acquisition, the protein synthesis inhibitor cycloheximide (CHX) was administered intraperitoneally. Fear sensitization to white noise and fear generalization to tones with frequencies differing from the conditioned tone were assessed at either 2 or 4 days after fear acquisition. Results: The results showed that, although varying shock intensities (except the lowest) led to a similar pattern of increased freezing during auditory cues in fear acquisition, the extent of both fear sensitization and generalization increased with the intensity of the footshock in the following days. As shock intensities increased, there was a proportional rise in sensitized fear to white noise and generalized freezing to tones with frequencies progressively closer to the conditioned stimulus. Mildest shocks did not induce discriminative conditioned fear memory, whereas the most intense shocks led to pronounced fear generalization. Administration of CHX before fear acquisition did not affect sensitized fear but reduced generalization of freezing to tones dissimilar from the conditioned stimulus in the group exposed to the most intense shock. Conclusions: Our results suggest that maladaptive fear responses elicited by varying stress intensities exhibit distinct characteristics. The effect of CHX to prevent overgeneralization without affecting discriminative fear memory points to potential therapeutic approaches for fear-related disorders, suggesting the possibility of mitigating overgeneralization while preserving necessary fear discrimination. [ABSTRACT FROM AUTHOR]
Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Fear generalization modulated by shock intensity and protein synthesis inhibitor.
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  Data: <searchLink fieldCode="AR" term="%22Dong%2C+Xinwen%22">Dong, Xinwen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Yunyun%22">Wang, Yunyun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Yudan%22">Liu, Yudan</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Li%2C+Yonghui%22">Li, Yonghui</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Dec2024, Vol. 241 Issue 12, p2627-2637. 11p.
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  Data: <searchLink fieldCode="DE" term="%22Generalized+anxiety+disorder%22">Generalized anxiety disorder</searchLink><br /><searchLink fieldCode="DE" term="%22Post-traumatic+stress+disorder%22">Post-traumatic stress disorder</searchLink><br /><searchLink fieldCode="DE" term="%22Stimulus+generalization%22">Stimulus generalization</searchLink><br /><searchLink fieldCode="DE" term="%22Protein+synthesis%22">Protein synthesis</searchLink><br /><searchLink fieldCode="DE" term="%22White+noise%22">White noise</searchLink><br /><searchLink fieldCode="DE" term="%22Sensitization+%28Neuropsychology%29%22">Sensitization (Neuropsychology)</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Rationale: Maladaptive fear responses, including sensitized threat reactions and overgeneralization, contribute to anxiety disorders such as generalized anxiety disorder and post-traumatic stress disorder. Although stress intensity influences the generation and extent of these maladaptive fears, the underlying mechanisms remain unclear. Objectives: The present study examined whether varying footshock stress intensity and inhibition of protein synthesis have differential effect on fear sensitization and generalization in mice. Methods: Mice were subjected to a classic fear conditioning protocol involving five different levels of footshock intensities. Prior to fear acquisition, the protein synthesis inhibitor cycloheximide (CHX) was administered intraperitoneally. Fear sensitization to white noise and fear generalization to tones with frequencies differing from the conditioned tone were assessed at either 2 or 4 days after fear acquisition. Results: The results showed that, although varying shock intensities (except the lowest) led to a similar pattern of increased freezing during auditory cues in fear acquisition, the extent of both fear sensitization and generalization increased with the intensity of the footshock in the following days. As shock intensities increased, there was a proportional rise in sensitized fear to white noise and generalized freezing to tones with frequencies progressively closer to the conditioned stimulus. Mildest shocks did not induce discriminative conditioned fear memory, whereas the most intense shocks led to pronounced fear generalization. Administration of CHX before fear acquisition did not affect sensitized fear but reduced generalization of freezing to tones dissimilar from the conditioned stimulus in the group exposed to the most intense shock. Conclusions: Our results suggest that maladaptive fear responses elicited by varying stress intensities exhibit distinct characteristics. The effect of CHX to prevent overgeneralization without affecting discriminative fear memory points to potential therapeutic approaches for fear-related disorders, suggesting the possibility of mitigating overgeneralization while preserving necessary fear discrimination. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.1007/s00213-024-06662-1
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              Text: Dec2024
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              Y: 2024
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