Genetic independence of mouse measures of some aspects of novelty seeking

Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon, United States
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 04/2006; 103(13):5018-23. DOI: 10.1073/pnas.0509724103
Source: PubMed


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.

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    • "Phenotypic differences in susceptibility to stress associated with differences in responses to natural and drug rewards were also reported [32]. Because all same-sex members of inbred strains are genetically identical, when animals belonging to same strain are tested under controlled conditions, individual differences among animals have to reflect allelic and functional differences probably modulated by prenatal and postnatal environmental factors or early dominance hierarchies [79]–[81]. Although environmental influences determining the phenotypic variability in inbred subjects are difficult to control and measure, inbred mice raised in rigorously defined environments may show variability in some traits unrelated to genetic and environmental influences [82]. "
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    ABSTRACT: Approach or avoidance behaviors are accompanied by perceptual vigilance for, affective reactivity to and behavioral predisposition towards rewarding or punitive stimuli, respectively. We detected three subpopulations of C57BL/6J mice that responded with avoiding, balancing or approaching behaviors not induced by any experimental manipulation but spontaneously displayed in an approach/avoidance conflict task. Although the detailed neuronal mechanisms underlying the balancing between approach and avoidance are not fully clarified, there is growing evidence that endocannabinoid system (ECS) plays a critical role in the control of these balancing actions. The sensitivity of dorsal striatal synapses to the activation of cannabinoid CB1 receptors was investigated in the subpopulations of spontaneously avoiding, balancing or approaching mice. Avoiding animals displayed decreased control of CB1 receptors on GABAergic striatal transmission and in parallel increase of behavioral inhibition. Conversely, approaching animals exhibited increased control of CB1 receptors and in parallel increase of explorative behavior. Balancing animals reacted with balanced responses between approach and avoidance patterns. Treating avoiding animals with URB597 (fatty acid amide hydrolase inhibitor) or approaching animals with AM251 (CB1 receptor inverse agonist) reverted their respective behavioral and electrophysiological patterns. Therefore, enhanced or reduced CB1-mediated control on dorsal striatal transmission represents the synaptic hallmark of the approach or avoidance behavior, respectively. Thus, the opposite spontaneous responses to conflicting stimuli are modulated by a different involvement of endocannabinoid signaling of dorsal striatal neurons in the range of temperamental traits related to individual differences.
    PLoS ONE 03/2012; 7(3):e33260. DOI:10.1371/journal.pone.0033260 · 3.23 Impact Factor
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    • "A recent review has suggested that the effects of anxiolytic compounds on head-dipping behaviour are generally confounded by changes in overall locomotion, despite the claims that head-dipping is unrelated to locomotor activity (Kliethermes and Crabbe, 2006a). Similarly, a study of several inbred mouse strains reported that head-dipping and locomotion are highly correlated (Kliethermes and Crabbe, 2006b). Whether head-dipping can be interpreted as a valid measure of neophilia remains unresolved (Bilkei-Gorzó and Gyertyán, 1996; Renner, 1990). "
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    ABSTRACT: The exploratory behaviour of laboratory rodents is of interest within a number of areas of behavioural pharmacology. However, how best to measure exploratory behaviour in rodents remains a contentious issue. Many unconditioned tests, such as the open field, potentially confound general locomotor activity with exploration. The hole-board apparatus appears to avoid this confound, as head-dipping into holes in the floor is assumed to be a valid measure of the subject's attraction towards novelty (neophilia). This study aimed to investigate whether head-dipping should be considered a valid measure of neophilia by comparing performance of adult male and female Lister hooded rats on the hole-board task (a) over repeated sessions and (b) when novel objects were absent or present underneath the holes. The results show that head-dipping initially decreased across repeated exposures, while time spent in the aversive central area increased. No change in head-dipping was seen in response to objects being placed underneath the holes. Rather than being a measure of neophilia, these results support the hypothesis that head-dipping represents an escape response, which declines as the subject becomes less fearful. These results are compared with previous studies of repeated exposure to other novel environments.
    Behavioural Processes 08/2008; 78(3):442-8. DOI:10.1016/j.beproc.2008.02.019 · 1.57 Impact Factor
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    • "Route-tracing stereotypy scores are not correlated with overall locomotor activity An important issue that would limit the utility of the preceding t-pattern approach would be if increased locomotor activity itself (and the concomitant increase in overall detected patterns) led to a larger route-tracing stereotypy score. 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 homecage data to normalize locomotor speeds without altering mouse locomotor paths. "
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    ABSTRACT: Route-tracing stereotypy is a powerful behavioral correlate of striatal function that is difficult to quantify. Measurements of route-tracing stereotypy in an automated, high throughput, easily quantified, and replicable manner would facilitate functional studies of this central nervous system region. We examined how t-pattern sequential analysis (Magnusson Behav Res Meth Instrum Comput 32:93-110, 2000) can be used to quantify mouse route-tracing stereotypies. This method reveals patterns by testing whether particular sequences of defined states occur within a specific time interval at a probability greater than chance. Mouse home-cage locomotor patterns were recorded after psychostimulant administration (GBR 12909, 0, 3, 10, and 30 mg/kg; d-amphetamine, 0, 2.5, 5, and 10 mg/kg). After treatment with GBR 12909, dose-dependent increases in the number of found patterns and overall pattern length and depth were observed. Similar findings were seen after treatment with d-amphetamine up to the dosage where focused stereotypies dominated behavioral response. For both psychostimulants, detected patterns displayed similar morphological features. Pattern sets containing a few frequently repeated patterns of greater length/depth accounted for a greater percentage of overall trial duration in a dose-dependant manner. This finding led to the development of a t-pattern-derived route-tracing stereotypy score. Compared to scores derived by manual observation, these t-pattern-derived route-tracing stereotypy scores yielded similar results with less within-group variability. These findings remained similar after reanalysis with removal of patterns unmatched after human scoring and after normalization of locomotor speeds at low and high ranges. T-pattern analysis is a versatile and robust pattern detection and quantification algorithm that complements currently available observational phenotyping methods.
    Psychopharmacology 04/2008; 196(4):591-602. DOI:10.1007/s00213-007-0994-6 · 3.88 Impact Factor
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