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PubMed1994

Analysis of two measures of paw preference in a large population of inbred mice.

Two measures of lateralized forelimb usage, the Collins paw preference test and the Lateral Paw Preference test (LPP), were tested in 693 mice of 29 inbred strains and F1 crosses, and 2 embryo transfer groups. These strains included NZB, SM, and the NXSM recombinant inbred (RI) strains; RF and the NXRF RI strains; BXSB and the Y-consomic BXSB-Yaa+; DBA/2 and F1s of DBA/2 and BXSB and BXSB-Yaa; and NZB x NZW F1s. The findings indicated that (1) the Collins and LPP tests were independent in terms of direction of lateralization, (2) there were significant population biases of 60.96% rightward on the LPP test, and 54.39% leftward on the Collins test, (3) there were significant strain differences on measures of absolute asymmetry on both tests, (4) there were strain differences for direction of asymmetry on the Collins test, but not on LPP, (5) on the basis of the NXSM RI strains, 3 genetic loci contribute to strength of laterality on the LPP test, and (6) there was a strong correlation among strain means for strength of lateralization on the two tests. These results extend previous findings on the strength and direction of laterality, showing that two independent systems for direction of laterality may depend on the same mechanism for magnitude, and establish that multiple factors of handedness, previously identified in humans and other primates, also exist in mice.

Animals↗
PubMedDate not supplied

Behavioral Teratology: What's Not in a Name: A reply to Cattabeni and Abbracchio.

A recent critique of behavioral teratology by Cattabeni and Abbracchio stated four principle criticisms of the field. These were, first, that the documented effects in the literature in this field are poorly understood and may not represent genuine cases of adverse effects upon the progeny. Second, that the field is filled with suspect 'positives' as evidenced by the long list of agents identified as behavioral teratogens. Third, that the term 'behavioral teratology' defines itself in terms of "subtle behavioral effects [occurring] in the absence of overt signs of neurotoxicity." Fourth, that 'behavioral teratology' is a misnomer. First, the assertion that most of the effects in this field are unknown as to whether they are beneficial or adverse is untrue. Most of the effects observed in experimental animals can be compared to those in humans and to established developmental neurotoxins (positive controls). Second, the number of agents identified as behavioral teratogens in experimental animals is not an indication that the methods in the field are flawed. More agents have been identified experimentally as behavioral teratogens than have been confirmed or disconfirmed in humans partly due to a lack of adequate data in humans and partly because behavioral teratogenicity obeys the same principle as occurs in all fields of toxicology, i.e., dose-dependency. Since many of the identified effects are observed at dosages many times those to which humans are exposed, just as occurs for teratogenicity, carcinogenicity, and mutagenicity, this is not an indication of flawed methodology. Third, the notion that behavioral teratogenesis is defined in terms of 'subtle' effects is refuted by examining recent reviews.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed2004

Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks.

The present study, examines some issues in the measure and analysis of behavior in animals. Two strains of rats of both genders were used to illustrate and discuss these issues. We examined to what extent various behavioral measures reflect different or identical emotional or cognitive factors and, how sensitive are the various parameters of a task to differences between strains and genders. Wistar and Lister males and females rats were tested in an anxiety test then in the object recognition task followed by the object location task. Taking advantage of a simple computer program it is possible to: (1) record several parameters of theses tasks and examine the pattern of animal responses toward novelty and/or familiarity; (2) examine whether different measurements of the same response would reflect anxiety response to novelty and, can they discriminate between novelty and familiarity responses to objects; and (3) examine if changes in the pattern of animal responses are reflected by these measurements and, whether anxiety or discrimination is evident mainly during the first minute of the test. The results on the anxiety test show that different measures of the same response proved concordant and revealed significant differences between Lister males and Wistar males. Lister males approached more frequently an object and spent more time on an object in each approach compared to Wistar males in the first 5 min of test and in the total 10 min. They have also shorter latencies between approaches compared to Wistar males. The examination of performance over different time bins was significant with the measure of frequency. Lister male rats approached less frequently the object in the last 5 min of the test compared to the first 5 min. Their performance, however, did not differ from that of the other groups in this last 5 min. In the memory tasks, the measure of the frequency of approaches suggests that Lister male rats were able to discriminate between novel and familiar objects and, between novel and familiar location of objects. The measure of latency of first approach shows that Wistar female rats were able to discriminate between objects only in the spatial memory test. Discrimination in the object recognition task was observed in the first and second minute, and in the total 3 min sessions. Discrimination in the object location task was observed with the measure of frequency of approaches, in the first minute, and in the total 3 min sessions. Results from the total 3 min sessions were more concordant between the different measures of discrimination than results from separate 1 min bins. The results from the two memory tasks show that novelty prevented habituation to re-exposure to the testing environment. In many cases, novelty increased exploration of the objects in the choice phase compared to the sample phase. However, this lack of habituation or increased exploration in the choice phase is not concordant with most results of discrimination between novelty and familiarity from the same type of measurements.

Analysis of Variance↗
PubMed2004

Inter-individual vs line/strain differences in psychogenetically selected Roman High-(RHA) and Low-(RLA) Avoidance rats: neuroendocrine and behavioural aspects.

Inter-individual differences in neuroendocrine and behavioural responses to environmental challenges will be considered within the context of psychogenetic selection, using the Roman High-(RHA) and Low-(RLA) Avoidance rat lines as an example. We assume that the selected genotypes, by interacting with environmental factors, determine specific 'biobehavioural profiles'. Practical and theoretical problems regarding the measurement of inter-individual vs line/strain differences, the definition of 'traits' vs experimental variables, and possible correlations between physiological and behavioural parameters will be discussed. We will argue that environmental influences are the main cause of inter-individual variability, and that the genotype only constitutes a 'blueprint' from which typical biobehavioural profiles are established, notably under the influence of early environmental factors. These biobehavioural profiles may correspond in part to human categories known as 'types', 'temperaments' or 'personality traits'. Within each category (including those which can be obtained by psychogenetic selection), more individual personality traits can evolve, notably as a result of social interactions and particular life events.

Animals↗
PubMed2006

Behavioral phenotyping of mice lacking the K ATP channel subunit Kir6.2.

ATP-sensitive potassium (K(ATP)) channels are expressed in various tissues and cell-types where they act as so-called metabolic sensors that couple metabolic state to cellular excitability. The pore of most K(ATP) channel types is built by Kir6.2 subunits. Analysis of a general Kir6.2 knockout (KO) mouse has identified a variety of different functional roles for central and peripheral K(ATP) channels in situations of metabolic demand. However, the widespread distribution of these channels suggests that they might influence cellular physiology and animal behavior under metabolic control conditions. As a comprehensive behavioral description of Kir6.2 KO mice under physiological control conditions has not yet been carried out, we subjected Kir6.2 KO and corresponding wild-type (WT) mice to a test battery to assess emotional behavior, motor activity and coordination, species-typical behaviors and cognition. The results indicated that in these test situations Kir6.2 KO mice were less active, had impaired motor coordination, and appeared to differ from controls in their emotional reactivity. Differences between KO and WT mice were generally attenuated in test situations that resembled the home cage environment. Moreover, in their home cages KO mice were more active than WT mice. Thus, our results suggest that loss of Kir6.2-containing K(ATP) channels does affect animal behavior under metabolic control conditions, especially in novel situations. These findings assign novel functional roles to K(ATP) channels beyond those previously described. However, according to the widespread expression of K(ATP) channels, these effects are complex, being dependent on details of test apparatus, procedure and prior experience.

Analysis of Variance↗
PubMed2006

Endophenotypes for psychiatric disorders: ready for primetime?

It is increasingly accepted that the imprecision of categorical psychiatric diagnoses can be a limiting factor in understanding the genetic basis of human behavioral abnormalities. Genetic investigation of endophenotypes--more precisely defined quantitative traits hypothesized to underlie disease syndromes--offers great promise as an alternative or complement to studies of categorical disease phenotypes. However, there is not yet standardization of the methods by which candidate endophenotypes should be chosen and applied. Fruitful endophenotype studies depend on the selection of heritable, quantitative traits that can be objectively and reliably measured. In this article, we propose guidelines for such investigations for psychiatric disorders, using endophenotypes previously proposed for bipolar disorder as particular examples. Gene expression studies and non-human primate models are recent developments in which an endophenotype approach might prove particularly valuable.

Bipolar Disorder↗
PubMed2001

The use of behavioral test batteries: effects of training history.

Our laboratory uses a specific test battery for the initial assessment of phenotypic behavioral differences of transgenic, knockout, and inbred strains of mice. Our standard battery includes: open field activity, light-dark exploration, rotarod, prepulse inhibition (PPI), acoustic startle habituation, conditioned fear, Morris water maze, and hot plate. Tests are run in the order listed, from least invasive to most invasive, to decrease the chance that behavioral responses are altered by prior test history. The studies presented here were designed around two questions. The first study asks if differences exist between mice that have undergone testing on different tasks and mice that are naïve to the test experience. The second study asks if the test order affects how an animal performs on subsequent tests. In the first experiment, C57BL/6J male mice were evaluated on all of the tests described above. The behavior of these 'test battery' mice was compared to aged matched naïve mice that were only tested on one test from the battery. Results indicate that on some tests, the behavior of 'test battery' mice was significantly different from the behavior of naïve mice, while on other tests there were no differences. For example, test battery mice responded differently in the open-field, rotarod, and hot-plate test, but behaved similar on the PPI and conditioned fear. Experiments in the second study were performed on male 129/SvEvTac (129S6) and C57BL/6J male mice. An abbreviated battery of tasks was used and the results suggest that certain test variables are sensitive to test order, whereas others are resistant. These two studies demonstrate that some behavioral tests appear to be sensitive to previous testing experience, while other tests are immune.

Animals↗