title: Performance of F2 B6x129 hybrid mice in the Morris water maze, latent inhibition and prepulse inhibition paradigms: Comparison with C57Bl/6J and 129sv inbred mice.
abstract: Assessment of cognition and information processing in mice is an important tool in preclinical research that focuses on the development of cognitive enhancing drugs. Analysis of transgenic (TG) and knockout (KO) mice is usually performed on a F2 B6x 129 background. In the present study, we have compared performance of F2 B6x 129 hybrid mice (F2 mice) with that of the two parental inbred strains (C57Bl/6J and 129sv mice), and a wild-type (WT) strain (with a combined B6x 129 background) in three cognitive/information processing paradigms. It was found that the F2 mice outperformed either of the parental strains and provide a control sample with good baseline performance in the Morris water maze (MWM). Reliable deficits could be obtained in learning and memory in this paradigm following injections with scopolamine (0.16 mg/kg) in the F2 mice, which can potentially be used to test effects of reference and novel compounds in order to develop cognitive enhancing drugs. Furthermore, it was shown that the four genotypes showed normal latent inhibition (LI) using the conditioned taste aversion (CTA) paradigm and exhibited no differences in prepulse inhibition (PPI) levels. Following the setup of these procedures in mice, we are now able to compare the effects of gene knockout/mutations used for target validation with results in the present study as a frame of reference.
authors.affiliation: Johnson and Johnson, Pharmaceutical Research and Development (J and J PRD), CNS Discovery Research, Beerse, Belgium. natasja.debruin@solvay.com
authors.forename: Natasja
authors.initials: N
authors.lastname: de Bruin
authors.forename: Michel
authors.initials: M
authors.lastname: Mahieu
authors.forename: Tarah
authors.initials: T
authors.lastname: Patel
authors.forename: Roland
authors.initials: R
authors.lastname: Willems
authors.forename: Anne
authors.initials: A
authors.lastname: Lesage
authors.forename: Anton
authors.initials: A
authors.lastname: Megens
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000502:physiology; D005838:Genotype; D018021:Lithium Chloride / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000502:physiology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D013216:Reflex, Startle / Q000502:physiology*; D012201:Reward; D012601:Scopolamine / Q000494:pharmacology; D013028:Space Perception / Q000502:physiology; D013045:Species Specificity; D013395:Sucrose; D013649:Taste
chemical_list: D018692:Antimanic Agents; D018727:Muscarinic Antagonists; D013395:Sucrose; D012601:Scopolamine; D018021:Lithium Chloride