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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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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: 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