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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: The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors.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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Short- and long-term recall of cued conditioned fear in HAB and NAB mice.CS only was presented to separate HAB and NAB groups 1 h, 6 h (short-term) or 24 h (long-term) after cued fear conditioning. Irrespective of consolidation period, HAB mice showed pronounced freezing during the fear expression test, but not NAB mice. Data are presented as means ± SEM. n = 6–8 per experimental group. ***p<0.001 HAB vs. NAB.
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pone-0016849-g003: Short- and long-term recall of cued conditioned fear in HAB and NAB mice.CS only was presented to separate HAB and NAB groups 1 h, 6 h (short-term) or 24 h (long-term) after cued fear conditioning. Irrespective of consolidation period, HAB mice showed pronounced freezing during the fear expression test, but not NAB mice. Data are presented as means ± SEM. n = 6–8 per experimental group. ***p<0.001 HAB vs. NAB.

Mentions: In all experiments performed to investigate short-term recall of cued conditioned fear, HAB and NAB animals were conditioned within five CS-US pairings to the same extent (data not shown). As with the 24 h period, expression of cued conditioned fear differed greatly between HAB and NAB mice 1 h (t = 15.220, df = 12, p<0.001) and 6 h (t = 12.825, df = 12, p<0.001) after the fear conditioning (Figure 3). There was no significant effect of testing period on fear-expression levels (F2,42 = 2.475, p = 0.096; Figure 3).


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)

Short- and long-term recall of cued conditioned fear in HAB and NAB mice.CS only was presented to separate HAB and NAB groups 1 h, 6 h (short-term) or 24 h (long-term) after cued fear conditioning. Irrespective of consolidation period, HAB mice showed pronounced freezing during the fear expression test, but not NAB mice. Data are presented as means ± SEM. n = 6–8 per experimental group. ***p<0.001 HAB vs. NAB.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0016849-g003: Short- and long-term recall of cued conditioned fear in HAB and NAB mice.CS only was presented to separate HAB and NAB groups 1 h, 6 h (short-term) or 24 h (long-term) after cued fear conditioning. Irrespective of consolidation period, HAB mice showed pronounced freezing during the fear expression test, but not NAB mice. Data are presented as means ± SEM. n = 6–8 per experimental group. ***p<0.001 HAB vs. NAB.
Mentions: In all experiments performed to investigate short-term recall of cued conditioned fear, HAB and NAB animals were conditioned within five CS-US pairings to the same extent (data not shown). As with the 24 h period, expression of cued conditioned fear differed greatly between HAB and NAB mice 1 h (t = 15.220, df = 12, p<0.001) and 6 h (t = 12.825, df = 12, p<0.001) after the fear conditioning (Figure 3). There was no significant effect of testing period on fear-expression levels (F2,42 = 2.475, p = 0.096; Figure 3).

Bottom Line: The propensity to develop an anxiety disorder is thought to be determined by genetic and environmental factors.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