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PubMed1993

Evidence for and against the Naples high- and low-excitability rats as genetic model to study hippocampal functions.

The Naples high- (NHE) and low-excitability (NLE) are two rat lines, selectively bred for high and low activity levels in a Làt-maze, respectively. Because the activity level in a novel environment depends mainly on the integrity of the hippocampal formation, and NLE and NHE rats differ with a similar background of emotionality, arterial blood pressure, and learning ability, they have been proposed as animal model to study hippocampal functions. Our aim is to prove evidence in favor and against this hypothesis. The evidence in favor indicates that NLE/NHE rats have a defective spatial processing, and pertains to (a) Differential activity in a spatial novelty situation (selection trait), proportional to the stimulus complexity rats are exposed to (NHE are hyper- and NLE-rats hypoactive); and (b) Impaired working memory in a six-arm non-reinforced tunnel maze in both lines compared to random-bred rats, that was reversed by the introduction of a reinforcer. In addition, multiple evidence of (i) lower intra- + infrapyramidal mossy fiber terminals in both NLE/NHE vs. controls; (ii) increased sensitivity of hippocampal elements to microinjections of vasopressin (but not oxytocin) and of "delta" (but not "mu") opioids; (iii) lower number of high-affinity glucocorticoid receptors; (iv) lower number of alpha- but not beta-adrenergic receptors in the hippocampus and hypothalamus of NHE rats only; and (v) the genotype-dependent behavior of a DNA fraction with fast turnover, suggest that both NHE/NLE are "disintegrated" at the hippocampal interface. Further, neurobehavioral covariations among individual differences reveal nonlinear, complex relationships, an evidence apparently against the hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2002

The sliding window correlation procedure for detecting hidden correlations: existence of behavioral subgroups illustrated with aged rats.

We developed the sliding window correlation procedure in order to examine populations for possible heterogeneity in the ways two variables are related with each other. This procedure involves computing correlation coefficients (R) for overlapping successive segments of the covariate scores. The distribution of resulting Rs reveals fluctuations in the degree and direction of R over the sample of ranked scores. This procedure is applied to behavioral data of aged rats, which were rank-ordered according to water maze performance, and correlated with open field exploration and conflict behavior in a light/dark chamber. Results revealed correlation coefficients of varying magnitudes and opposing directions for different segments of the population, which were obscured by overall correlation analysis. E.g. for the superior learners, the Rs were highest between maze learning ability, increased open field exploration and reduced anxiety in the conflict test, whereas for the intermediate learners the Rs were highest for maze learning ability related with reduced exploration and increased anxiety. Thus, the sliding window correlation distribution can be applied in conjunction with overall correlation analysis to provide information about the potential presence and locations of subgroups within a population, especially if overall correlation analysis does not yield significant results.

Aging↗
PubMed1998

IL-6 deficiency leads to increased emotionality in mice: evidence in transgenic mice carrying a null mutation for IL-6.

The role of interleukin-6 (IL-6) on emotional behavior was studied in two experiments using transgenic mice carrying a null mutation for IL-6 (IL-6(-/-)). In the first experiment, IL-6(-/-) mice were compared with the two wild-type strains contributing to the genetic background of the transgenic mice, namely C57BL/6J and 129/SvJ, as well as with the F2 offspring of C57BL/6J x 129/SvJ mice. The two parental strains differed substantially in terms of emotional reactivity, suggesting that the F2 offspring were more appropriated for analyzing the effect of the null mutation. IL-6(-/-) mice showed lower levels of ambulation in the holeboard, and lower levels of exploration of the open arms of the plus-maze, than the wild-type F2 C57BL/6J x 129/SvJ mice. In the second experiment, IL-6(-/-) mice were backcrossed for 10 generations to C57BL/6J mice to decrease the uncertainty of the effect of the genetic background, and when compared with wild-type C57BL/6J mice in the holeboard and the plus-maze, the same results were obtained. Therefore, IL-6(-/-) mice seem to be more emotional than their appropriate controls, suggesting that the major cytokine IL-6 is involved in the control of emotionality.

Animals↗
PubMed2000

Ethological confirmatory factor analysis of anxiety-like behaviour in the murine elevated plus-maze.

The elevated plus-maze has been used in animal research to measure anxiety since 1985 and is currently the most widely used animal model of anxiety. Since this paradigm has been the subject of several principal components analyses, it is well qualified for confirmatory factor analysis research. The current report builds on the substantial theoretical knowledge and empirical data obtained from these structural analyses with a view to obtain further progress in the evolution of our understanding of animal anxiety in the elevated plus-maze. The purpose of the present report was two-fold: (a) to test if the a piori imposition of a 3-factor model, or a competing 2-factor elevated plus-maze model, would fit our sample (n=200 CD-1 mice) data in each of two trials within an inferential confirmatory factor analytic framework; (b) provide a well-fitting model that confers indicator variables that can most effectively and parsimoniously measure underlying constructs of elevated plus-maze behaviour. Multiple model-fitting criteria were used, and issues related to data non-normality, outliers, replicability of the model, sampling error and error of approximation in the estimation of final model fit were addressed. The final 2-factor model, with estimated error covariance between two different pairs of indicator variables, was a good fit on the trial-1 data, although it was necessary to allow unprotected stretch attends to non-significantly cross-load on factor-2. A 2-factor model also fit the trial-2 data from the present analysis, although it was necessary to allow closed arm time ratio to negatively cross-load on factor-1. These results indicate that inferential hypothesis testing and model building procedures within a confirmatory factor analysis framework produces interpretable animal anxiety indices in the elevated plus-maze. Moreover, a 2-factor, rather than a 3-factor model, parsimoniously and unambiguously explained the underlying constructs of anxiety-like mouse behaviour in the elevated plus-maze in the present study. Taken together, a reduction in the growing number of behavioural indices reported in elevated plus-maze pharmacological studies is suggested.

Animals↗
PubMed2002

Amygdala or ventral hippocampal lesions at two early stages of life differentially affect open field behaviour later in life; an animal model of neurodevelopmental psychopathological disorders.

Psychiatric disorders like schizophrenia or autism are thought to result from disruption of the normal pattern of brain development. Abnormalities in the amygdaloid complex and hippocampus have been reported in these disorders. In the present study rats were lesioned in the amygdala or ventral hippocampus on day 7 of life (immature brain) or day 21 of life (almost mature brain) and open field behaviour was determined later in life before and after puberty. Lesioning on day 7 resulted in behavioural changes, interpreted as locomotor stereotypy and decreased anxiety in case of amygdala or hippocampus, respectively. These effects were more profoundly present after puberty. Lesioning on day 21 did not result in these behavioural changes, which subscribes to the importance of the stage of brain maturation on functional development. The results suggest that the behavioural changes in rats lesioned on day 7 may due to a malfunctioning of structures connected to the amygdala or ventral hippocampus. Brain lesions made on day 7 of life may serve as a potential model of psychopathological neurodevelopmental disorders.

Aging↗
PubMed2002

Evaluation of the elevated plus-maze and open-field tests for the assessment of anxiety-related behaviour in inbred mice.

The elevated plus-maze test (PM) and open-field test (OF) are routinely used to study anxiety-related behaviour in mouse. However, the data obtained with these tests have often been contradictory, probably because of differences between laboratories in the selection and analysis of behavioural parameters. We have characterised the pattern of mouse anxiety by analysing a number of behavioural parameters with both PM and OF in BALB/c and C57BL/6 mice, two behaviourally distant mouse strains. Twenty-eight variables (15 analysed with PM and 13 with OF) were selected by correlation analysis from those initially recorded with both tests. The scores of the selected variables were first analysed by MANOVAs, and then by principal component analysis (PCA). PCA extracted five factors for PM and four factors for OF. These factors were subjected to a correlation analysis, which showed significant correlation between four of them. The factorial scores of BALB/c and C57BL/6 mice were analysed by MANOVAs, which showed significant effects of both the strain and test used. Our results confirm the multidimensional structure of mouse anxiety-related behaviour as regards both simple components and functional interactions, and comprehensively represent strain- and test-specific features of mouse anxiety-related behaviour.

Animals↗
PubMed2003

Estradiol valerate and alcohol intake: a comparison between Wistar and Lewis rats and the putative role of endorphins.

Studies show that estrogens can influence alcohol consumption; however, findings are variable and an etiology remains unknown. Furthermore, estrogen administration can alter several neurotransmitter systems implicated in alcohol consumption, including the beta-endorphin (beta-EP) system. The present studies investigate (a) whether estradiol valerate (EV) alters voluntary alcohol consumption in Wistar and Lewis rats, (b) if an effect of EV on drinking is associated with changes in hypothalamic or pituitary beta-EP content, and (c) whether differences in alcohol drinking between treatment and rat groups are related to locomotor or defensive behavior/anxiety scores. Of 30 Wistar and 30 Lewis rats used in this study, half were injected with 2 mg EV in 0.2 ml sesame oil, while the remainder were injected with the vehicle only. After 8 weeks, all animals were tested in the open field and elevated plus maze. A week later, 4-6 animals in each group were sacrificed. The remaining animals were tested for voluntary alcohol drinking for 24 days prior to being sacrificed on the last day. Radioimmunoassay was used to estimate hypothalamic and pituitary beta-EP content. Wistar and Lewis rats injected with EV showed an increase in alcohol drinking, but their behavior scores and beta-EP levels remained unaltered. This result suggests that any EV effect on drinking is unrelated to changes in beta-EP or behavioral performance. Furthermore, Wistar rats show higher alcohol drinking, locomotor and defensive behavior scores, and hypothalamic beta-EP than Lewis rats. Higher alcohol drinking by Wistar rats might be due to higher behavioral scores or endogenous opioid activity/sensitivity.

Alcohol Drinking↗
PubMed2003

Effects of medial prefrontal cortex cytotoxic lesions in mice.

Mice (C57BL/6J strain, females) with cytotoxic lesions of the medial wall of the prefrontal cortex were given a battery of tests to assess emotional, species-typical, cognitive, motor and other behaviours. Lesioned mice showed a profile of reduced anxiety, both on a plus-maze, and a similar, novel test, the successive alleys. There was no evidence, however, for attenuation of anxiety in tests of hyponeophagia, and lesioned mice, like controls, preferred the black to the white area of an enclosed alley. Their locomotor activity tended to be higher than that of the controls, particularly when the test surroundings were novel or relatively so. Species-typical behaviours were similar to those of control mice, except lesioned mice displaced ('burrowed') less food pellets from a tube in their home cage. They were not impaired at learning a spatial Y-maze reference memory task, which is profoundly affected by cytotoxic hippocampal lesions in the same strain, or at learning a multi-trial passive avoidance test. Their strength and co-ordination in motor performance tests was also normal. The results show that cytotoxic medial prefrontal cortex lesions in mice produce a clear but restricted anxiolytic action. The marked reduction in burrowing, in the absence of any detectable impairment of motor ability, demonstrates the sensitivity of this behavioural index.

Animals↗
PubMed2002

Home cage activity and behavioral performance in inbred and hybrid mice.

Locomotor activity is a key component in many behavioral tests, suggesting that genetic differences in activity levels may be a critical consideration when comparing mouse strains. In order to assess the relationship between activity and performance, we recorded home cage activity, and locomotion and defecation, a non-activity-linked behavior, in tests of anxiety in inbred (C57BL/6J (B6), n = 25; BALB/cJ (C), n = 24; DBA/2J (D2), n = 28) and hybrid (CB6F1/6J (CB6: B6 x C) n = 19) mice. Under our test conditions, the strains showed significant differences in home cage activity levels: C > B6 > D2. The CB6 mice were similar to the B6 mice in horizontal activity and were intermediate between the parental strains in vertical movement. Based on measures of locomotion and defecation in the open field, emergence and novel object tests, and the elevated zero maze, the C mice appeared to be the most anxious and the B6 were the least anxious. The D2 mice were intermediate on some measures but more similar to B6 mice on others, making ranking them more difficult. In addition, the CB6 mice displayed characteristics of both parental strains. They had greater similarity to B6 mice in measures of horizontal movement in the home cage and locomotion in the open field and emergence tests, but exhibited defecation responses similar to those of C mice in the novel object test and elevated zero maze. The results suggest that strain differences in spontaneous locomotion should be considered when interpreting strain differences in behavioral tests, and that home cage activity may be a useful interpretive aid.

Animals↗
PubMed1992

Unilateral lesion in the tuberomammillary nucleus region: behavioral asymmetries and effects of histamine precursor.

The subnuclei of tuberomammillary nucleus are located in the posterior part of the hypothalamus adjacent to the basolateral surface of the mammillary bodies. The neurons of this nucleus innervate extensive parts of the brain with several transmitters, particularly with histamine. In fact, they represent the only source of histaminergic projections in the brain. The present study deals with the effects of a lesion in this region on behavior. Unilateral electrolytic direct current (DC) lesions in the tuberomammillary nucleus led to an asymmetry in thigmotactic scanning; i.e., at 11 days, but not 1 day postlesion, the rats scanned the walls of an open field more with the vibrissae contralateral to the lesion than with those of the ipsilateral side. Furthermore, they emitted more ipsiversive than contraversive wide angle turns. The behavioral asymmetries are, in general, opposite in direction to those induced by lesion of the neighboring lateral hypothalamus and substantia nigra, indicating that they are specific to the tuberomammillary region destroyed. Application of the histamine precursor histidine led to a compensation of these asymmetries, suggesting that the tuberomammillary's histaminergic efferents are functionally related to the lesion-induced behavioral effects.

Animals↗
PubMed1992

Hippocampal mossy fibres: implication in novelty reactions or in anxiety behaviours?

Hippocampal mossy fibre distribution is known to correlate with various processes including responses to novelty. Unfortunately, these correlations have been calculated using behavioural variables recorded in situations including anxiogenic components and so it is not clear whether the hippocampal trait is related to novelty reactions or to anxiety. In order to better elucidate the functional role of the supra- (SP-MF), intra-infra-(IIP-MF) and dentate gyrus (CA4) mossy fibres synaptic area, we investigated their covariations with behavioural measures recorded in situations related to novelty (free exploration test, confrontation with a novel object) or to anxiety (light/dark choice test). The hippocampus-behaviour correlation matrix reveals that IIP-MF and SP-MF correlate with variables linked to novelty reactions while CA4 correlates with measures related to anxiety.

Animals↗
PubMed1992

A new one-trial test for neurobiological studies of memory in rats. III. Spatial vs. non-spatial working memory.

Rats were submitted to object and spatial recognition tests (both based on the same paradigm) and to the radial-arm maze. The results are as follows: (1) rats could discriminate between a new and a familiar object when the retention delay was 1 min, 15 min or 60 min but not 24 h. The relationship between the level of discrimination and intertrial delays is quadratic with a maximum for 15 min. (2) Exposure to distractive stimuli during the retention delay may impair object recognition. (3) Rats discriminated between a new and a familiar space. (4) There is no correlation between the three tests which argues for a multiple form of working memory, especially a spatial and a non-spatial one. (5) Medial septal lesion did not impair object and spatial recognition memory, but the level of discrimination in the spatial recognition test was significantly reduced compared to that of control.

Aging↗
PubMed1998

Investigative burying by laboratory mice may involve non-functional, compulsive, behaviour.

The burying activity levels of albino mice offered a glass marble and a living scorpion on different occasions, were compared with the levels of exploration/investigation, avoidance, and displacement activities the same subjects performed during these and two other tests, the latter involving exploration with no particular stimulus-object and displacement with locomotion impossible. Although different average response levels were expected to occur in the different tests, it was assumed that the levels of related behavioural patterns correlated over the variation of individual mice. The scorpion elicited more burying than the marble, but the inanimate stimulus-object caused more avoidance. Exploration produced the only consistent, positive, correlation with burying in both female and male subjects. Only negative correlation occurred in males between burying and displacement, suggesting that these were alternative, in part non-functional, patterns. In females and males, while both touching and avoiding the marble decreased with experience over days, burying and displacement did not. The main conclusion is that burying began as an appropriate, investigative, activity, but, following frustrated investigation of the non-reactive stimulus-object, persisted as a compulsive stereotypy in subjects lacking in general experience, as laboratory rodents are in comparison with wild conspecifics. A simple model of compulsive disorder is proposed, in which initially appropriate behaviour goes on with inappropriate repetition when it does not attain its aim and the subject has internal difficulty in finding alternative patterns.

Aggression↗