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Enhanced fear expression in a psychopathological mouse model of trait anxiety: pharmacological interventions.

Sartori SB, Hauschild M, Bunck M, Gaburro S, Landgraf R, Singewald N - PLoS ONE (2011)

Bottom Line: These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line.The enhanced fear response of HAB mice was attenuated by treatment with either the α(2,3,5)-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429.Overall, the HAB mouse line may represent an interesting model (i) for identifying biological factors underlying misguided conditioned fear responses and (ii) for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Center for Molecular Biosciences Innsbruck and Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria. simone.sartori@uibk.ac.at

ABSTRACT
The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors. Here we investigated the relationship between a genetic predisposition to trait anxiety and experience-based learned fear in a psychopathological mouse model. Male CD-1 mice selectively bred for either high (HAB), or normal (NAB) anxiety-related behaviour on the elevated plus maze were subjected to classical fear conditioning. During conditioning both mouse lines showed increased fear responses as assessed by freezing behaviour. However, 24 h later, HAB mice displayed more pronounced conditioned responses to both a contextual or cued stimulus when compared with NAB mice. Interestingly, 6 h and already 1 h after fear conditioning, freezing levels were high in HAB mice but not in NAB mice. These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line. The enhanced fear response of HAB mice was attenuated by treatment with either the α(2,3,5)-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429. Overall, the HAB mouse line may represent an interesting model (i) for identifying biological factors underlying misguided conditioned fear responses and (ii) for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias.

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Related in: MedlinePlus

Cued conditioned fear in HAB and NAB mice during the light (A, B) and dark (C, D) phases of the circadian cycle.Both lines showed the same increasing conditioned responses to the CS-US presentations, as indicated by freezing levels during CS presentation (A, C). In contrast, compared with NAB mice, HAB mice showed more pronounced freezing levels in response to the CS only during fear expression performed 24 h later (B, D). Note that freezing levels prior CS presentation (pre-CS) were negligible indicating that there was no contextual fear component (B, D). Data are presented as means ± SEM. n = 7–11 per line. **p<0.01, ***p<0.001 HAB vs. NAB; §p<0.05, §§§p<0.001 fear expression vs. last CS-US pairing.
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pone-0016849-g002: Cued conditioned fear in HAB and NAB mice during the light (A, B) and dark (C, D) phases of the circadian cycle.Both lines showed the same increasing conditioned responses to the CS-US presentations, as indicated by freezing levels during CS presentation (A, C). In contrast, compared with NAB mice, HAB mice showed more pronounced freezing levels in response to the CS only during fear expression performed 24 h later (B, D). Note that freezing levels prior CS presentation (pre-CS) were negligible indicating that there was no contextual fear component (B, D). Data are presented as means ± SEM. n = 7–11 per line. **p<0.01, ***p<0.001 HAB vs. NAB; §p<0.05, §§§p<0.001 fear expression vs. last CS-US pairing.

Mentions: When animals were placed into the conditioning chamber for fear conditioning (Figures 1A and 2A) or into an empty mouse cage for cued fear expression (Figures 2B and D), the freezing behaviour was negligible in both HAB and NAB lines (<3%) indicating that there was no contextual fear component in cued auditory fear expression. No statistically significant difference between lines in baseline freezing to both contexts was observed.


Enhanced fear expression in a psychopathological mouse model of trait anxiety: pharmacological interventions.

Sartori SB, Hauschild M, Bunck M, Gaburro S, Landgraf R, Singewald N - PLoS ONE (2011)

Cued conditioned fear in HAB and NAB mice during the light (A, B) and dark (C, D) phases of the circadian cycle.Both lines showed the same increasing conditioned responses to the CS-US presentations, as indicated by freezing levels during CS presentation (A, C). In contrast, compared with NAB mice, HAB mice showed more pronounced freezing levels in response to the CS only during fear expression performed 24 h later (B, D). Note that freezing levels prior CS presentation (pre-CS) were negligible indicating that there was no contextual fear component (B, D). Data are presented as means ± SEM. n = 7–11 per line. **p<0.01, ***p<0.001 HAB vs. NAB; §p<0.05, §§§p<0.001 fear expression vs. last CS-US pairing.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046120&req=5

pone-0016849-g002: Cued conditioned fear in HAB and NAB mice during the light (A, B) and dark (C, D) phases of the circadian cycle.Both lines showed the same increasing conditioned responses to the CS-US presentations, as indicated by freezing levels during CS presentation (A, C). In contrast, compared with NAB mice, HAB mice showed more pronounced freezing levels in response to the CS only during fear expression performed 24 h later (B, D). Note that freezing levels prior CS presentation (pre-CS) were negligible indicating that there was no contextual fear component (B, D). Data are presented as means ± SEM. n = 7–11 per line. **p<0.01, ***p<0.001 HAB vs. NAB; §p<0.05, §§§p<0.001 fear expression vs. last CS-US pairing.
Mentions: When animals were placed into the conditioning chamber for fear conditioning (Figures 1A and 2A) or into an empty mouse cage for cued fear expression (Figures 2B and D), the freezing behaviour was negligible in both HAB and NAB lines (<3%) indicating that there was no contextual fear component in cued auditory fear expression. No statistically significant difference between lines in baseline freezing to both contexts was observed.

Bottom Line: These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line.The enhanced fear response of HAB mice was attenuated by treatment with either the α(2,3,5)-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429.Overall, the HAB mouse line may represent an interesting model (i) for identifying biological factors underlying misguided conditioned fear responses and (ii) for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Center for Molecular Biosciences Innsbruck and Institute of Pharmacy, University of Innsbruck, Innsbruck, Austria. simone.sartori@uibk.ac.at

ABSTRACT
The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors. Here we investigated the relationship between a genetic predisposition to trait anxiety and experience-based learned fear in a psychopathological mouse model. Male CD-1 mice selectively bred for either high (HAB), or normal (NAB) anxiety-related behaviour on the elevated plus maze were subjected to classical fear conditioning. During conditioning both mouse lines showed increased fear responses as assessed by freezing behaviour. However, 24 h later, HAB mice displayed more pronounced conditioned responses to both a contextual or cued stimulus when compared with NAB mice. Interestingly, 6 h and already 1 h after fear conditioning, freezing levels were high in HAB mice but not in NAB mice. These results suggest that trait anxiety determines stronger fear memory and/or a weaker ability to inhibit fear responses in the HAB line. The enhanced fear response of HAB mice was attenuated by treatment with either the α(2,3,5)-subunit selective benzodiazepine partial agonist L-838,417, corticosterone or the selective neurokinin-1 receptor antagonist L-822,429. Overall, the HAB mouse line may represent an interesting model (i) for identifying biological factors underlying misguided conditioned fear responses and (ii) for studying novel anxiolytic pharmacotherapies for patients with fear-associated disorders, including post-traumatic stress disorder and phobias.

Show MeSH
Related in: MedlinePlus