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Favoured genetic background for testing anxiolytics in the fear-potentiated and light-enhanced startle paradigms in the rat.
Behav Brain Res. 2011 Aug 01; 221(1):34-42.BB

Abstract

The fear-potentiated startle (FPS) and the light-enhanced startle (LES) paradigms are rodent tests of fear and anxiety, which combine face validity with predictive validity for clinically effective anxiolytic drugs. However, systematic strain comparisons aimed at identifying a rat strain that shows robust and reliable fear and anxiety responses in both models are missing. Here, we investigated four commonly used laboratory rat strains: Wistar, Sprague Dawley, Long-Evans and F344. Following strong cued fear conditioning training [60 conditioned stimulus-unconditioned stimulus (CS-US) pairings], all strains except Wistar exhibited significant FPS responses. F344 rats showed the strongest FPS response. Following milder cued fear conditioning protocols, designed to reduce the underlying component of contextual fear conditioning (by context pre-exposure or less CS-US pairings), also Wistar rats were able to show significant FPS, albeit still to a lesser extent than F344 rats tested under identical conditions. When tested in the LES protocol (light intensity ∼ 1500 lx), all strains except Long-Evans displayed significant light-enhanced startle responses. F344 and Wistar showed the strongest LES responses, which were of similar magnitude. The most sensitive strain in both paradigms, F344, was chosen for further pharmacological validation. The clinically active anxiolytic alprazolam (0.3, 1, 3mg/kg p.o.) dose-dependently reduced both fear-like responses in the FPS paradigm and anxiety-like responses in the LES paradigm at non-myorelaxant dosages. We propose that the F344 rat strain is particularly suited for the predictability assessment of novel anxiolytic drugs in both startle paradigms.

Authors+Show Affiliations

Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, 4123 Allschwil, Switzerland. michel.steiner@actelion.comNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Validation Study

Language

eng

PubMed ID

21354212

Citation

Steiner, Michel A., et al. "Favoured Genetic Background for Testing Anxiolytics in the Fear-potentiated and Light-enhanced Startle Paradigms in the Rat." Behavioural Brain Research, vol. 221, no. 1, 2011, pp. 34-42.
Steiner MA, Lecourt H, Rakotoariniaina A, et al. Favoured genetic background for testing anxiolytics in the fear-potentiated and light-enhanced startle paradigms in the rat. Behav Brain Res. 2011;221(1):34-42.
Steiner, M. A., Lecourt, H., Rakotoariniaina, A., & Jenck, F. (2011). Favoured genetic background for testing anxiolytics in the fear-potentiated and light-enhanced startle paradigms in the rat. Behavioural Brain Research, 221(1), 34-42. https://doi.org/10.1016/j.bbr.2011.02.021
Steiner MA, et al. Favoured Genetic Background for Testing Anxiolytics in the Fear-potentiated and Light-enhanced Startle Paradigms in the Rat. Behav Brain Res. 2011 Aug 1;221(1):34-42. PubMed PMID: 21354212.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Favoured genetic background for testing anxiolytics in the fear-potentiated and light-enhanced startle paradigms in the rat. AU - Steiner,Michel A, AU - Lecourt,Hugues, AU - Rakotoariniaina,Ando, AU - Jenck,Francois, Y1 - 2011/02/24/ PY - 2010/09/17/received PY - 2011/02/04/revised PY - 2011/02/12/accepted PY - 2011/3/1/entrez PY - 2011/3/1/pubmed PY - 2011/9/7/medline SP - 34 EP - 42 JF - Behavioural brain research JO - Behav Brain Res VL - 221 IS - 1 N2 - The fear-potentiated startle (FPS) and the light-enhanced startle (LES) paradigms are rodent tests of fear and anxiety, which combine face validity with predictive validity for clinically effective anxiolytic drugs. However, systematic strain comparisons aimed at identifying a rat strain that shows robust and reliable fear and anxiety responses in both models are missing. Here, we investigated four commonly used laboratory rat strains: Wistar, Sprague Dawley, Long-Evans and F344. Following strong cued fear conditioning training [60 conditioned stimulus-unconditioned stimulus (CS-US) pairings], all strains except Wistar exhibited significant FPS responses. F344 rats showed the strongest FPS response. Following milder cued fear conditioning protocols, designed to reduce the underlying component of contextual fear conditioning (by context pre-exposure or less CS-US pairings), also Wistar rats were able to show significant FPS, albeit still to a lesser extent than F344 rats tested under identical conditions. When tested in the LES protocol (light intensity ∼ 1500 lx), all strains except Long-Evans displayed significant light-enhanced startle responses. F344 and Wistar showed the strongest LES responses, which were of similar magnitude. The most sensitive strain in both paradigms, F344, was chosen for further pharmacological validation. The clinically active anxiolytic alprazolam (0.3, 1, 3mg/kg p.o.) dose-dependently reduced both fear-like responses in the FPS paradigm and anxiety-like responses in the LES paradigm at non-myorelaxant dosages. We propose that the F344 rat strain is particularly suited for the predictability assessment of novel anxiolytic drugs in both startle paradigms. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/21354212/Favoured_genetic_background_for_testing_anxiolytics_in_the_fear_potentiated_and_light_enhanced_startle_paradigms_in_the_rat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0166-4328(11)00125-2 DB - PRIME DP - Unbound Medicine ER -