Genetic independence of mouse measures of some aspects of novelty seeking

Abstract

High novelty seeking is a complex personality attribute correlated with risk for substance abuse. There are many putative mouse models of some aspects of novelty seeking, but little is known of genetic similarities among these models. To assess the genetic coherence of “novelty seeking,” we compared the performance of 14 inbred strains of mice in five tests: activity in a novel environment, novel environment preference, head dipping on a hole-board, object preference, and a two-trial version of the spontaneous alternation task. Differences among strains were observed for all tasks, but performance in any given task was generally not predictive of performance in any other. To evaluate similarities among these tasks further, we selectively bred lines of mice for high or low head dipping on the hole-board. Similar to results from the inbred strain experiments, head dipping was not correlated with performance in the other measures but was genetically correlated with differences in locomotor activity. Using two approaches to estimating common genetic influences across tasks, we have found little evidence that these partial models of novelty seeking reflect the influence of common genes or measure a single, unified construct called novelty seeking. Based on the substantial influence of genetic factors, ease of implementation, and relative independence from general locomotion, head dipping on a hole-board is a good task to use in the domain of novelty seeking, but multiple tasks, including others not tested here, would be needed to capture the full genetic range of the behavioral domain.

Development of a mouse test for repetitive, restricted behaviors: Relevance to autism

“…Previous work has shown that inbred mouse strains are characterized by different levels of head dipping in hole-board tasks [32,54]. Pharmacological assays have indicated that numbers of head dips can be increased by treatment with diazepam or other anxiolytic drugs, and decreased by anxiogenic compounds [75], although these changes may be related to general drug effects on activity levels [33].…”

“…We needed to find an optimal way to present up to 16 measures per test in a graphic form. In addition, as shown in Results, inbred mouse strains can have very different levels of nose poke responses (see also [32,54]), yet it would be beneficial to present the patterns of hole preference in a way that was comparable across strains or experimental groups. One way to control for the differences in numbers of nose pokes was to present the data as percent of total nose pokes per hole for each experimental group.…”

Variation in Mouse Basolateral Amygdala Volume is Associated With Differences in Stress Reactivity and Fear Learning

“…In a third test of anxiety-like behavior, the light-dark exploration test, the small and medium BLA groups spent less time in the light compartment and made fewer light-dark intercompartment transitions than the large BLA group. Different mouse tests for anxiety likely measure different forms of behavior controlled by distinct genetic factors (Turri et al, 1999;Holmes et al, 2003;Kliethermes and Crabbe, 2006) and it is possible that the profile of the small and medium BLA groups in the light-dark exploration test reflects a high anxiety-like phenotype that is not seen in the other tests. Taken together however, the differences between BLA volume groups on the anxiety-related assays (particularly the open-field and light-dark exploration tests) were marginal and are most parsimoniously interpreted as modest locomotor inhibition in response to novelty rather than a clear high anxiety-like phenotype in mice with smaller BLA volumes.…”

A novel method for automatic quantification of psychostimulant-evoked route-tracing stereotypy: application to Mus musculus

“…Investigating this is particularly challenging, as there are no pharmacological treatments known to fully dissociate changes in overall locomotor speed from the development of route-tracing stereotypies (e.g., Griebel et al 2000;Kliethermes and Crabbe 2006;Ohl et al 2001). As per the rationale described in "Materials and methods," we chose to mathematically transform home-cage data to normalize locomotor speeds without altering mouse locomotor paths.…”