Pierre Chapillon

Rearing environmental enrichment in two inbred strains of mice: 1. Effects on emotional reactivity.

The effects of an enriched rearing environment on two types of anxiety-like behavior (designated “trait” and “state” anxiety) and on spontaneous activity were investigated in two inbred strains of mice, BALB/c (C) and C57BL/6(B6). Subjects were socially reared from birth to 56 days of age under enriched or standard rearing conditions. The enriched environment consisted of an assembly of plastic boxes in which a various number of objects (running wheels, pieces of plastic, etc.) offered the possibility of multiple activities. The subjects were subsequently tested in three situations: a spontaneous activity recorder, an elevated plus-maze test (a model of state anxiety), and a free exploration test (a model of trait anxiety). No group differences could be found in spontaneous activity. Environmental enrichment, however, decreased the level of both types of anxiety-like behavior in the C strain. In contrast, the level of trait anxiety of the B6 mice was not modified. The results were discussed in relation to possible CNS modifications, especially in the limbic system.

Environmental enrichment in BALB/c mice : Effects in classical tests of anxiety and exposure to a predatory odor

Early stimulation by environmental enrichment generally leads to improved learning abilities in rodents. However, the effects of environmental enrichment on emotional reactivity remain more questionable and were mostly studied by using classical tests of anxiety based on confrontation with a novel environment. The main goal of our study was to use different tests of anxiety to compare BALB/c mice reared in either a standard condition (SC) or enriched condition (EC). Exposure to cat feces was used to assess anxiety according to an ethoexperimental approach and a comparison was made with the elevated plus maze and the open field as classical tests of anxiety. In accordance with previous works, our results show that EC mice were more active than SC mice in the elevated plus maze and the open field. Thus, possibly as a direct consequence of frequent changes in their breeding conditions, reactivity to a novel environment was reduced in EC mice. However, the cat odor test revealed no intergroup differences for behavior, although corticosterone levels were reduced in EC mice. These results indicate that classical (i.e. reaction to novel environments) and ethoexperimental-based tests (i.e. exposure to predator cues) measure different aspects of emotional reactivity. Further studies using ECs should be useful for the delineation of the neurobiological substrates of these different reactions.

Further evidences that risk assessment and object exploration behaviours are useful to evaluate emotional reactivity in rodents.

In this study, we tested the ability of risk assessment and exploration behaviours to emphasise PH effects. Indeed, postnatal handling (PH) decreases emotional reactivity in rats but inconsistent behavioural results can be observed and may be due to false negative (i.e. existing effects are not detected). Risk assessment behaviours were measured in the elevated plus maze, in the free exploration paradigm and in the open field. In addition, we measured object exploration behaviours towards familiar/new objects in the open field. PH increased general activity in the elevated plus maze and in the free exploration paradigm and risk assessment behaviours allowed demonstrating that these effects were specific to emotional reactivity. In the open field, PH increased object exploration as early as first exposition while general activity was unaffected. PH also decreased behavioural inhibition in response to the introduction of a novel object. On the whole, our results show that risk assessment and object exploration behaviours are valuable tools to measure more precisely emotional reactivity in rodents. This reinforces the idea that these behaviours should be used more frequently in order to avoid false negative when emotional reactivity changes are expected in unconditioned conflict tests.

Free versus forced exposure to an elevated plus-maze: evidence for new behavioral interpretations during test and retest

RationaleThe rodent elevated plus-maze is based on an approach/avoidance conflict between secure closed arms and aversive open arms that can be measured to assess anxiety. Despite this apparent simplicity, several discrepancies emerge from the interpretation of an animal’s behavior in the maze, especially when considering the one-trial tolerance effect.Objectives and methodsIn order to bring new elements of interpretation, we compared the behavior of rats exposed to the standard version of the test (forced exposure) to the behavior of rats that were allowed to freely explore the apparatus. We also compared the effects of testing/retesting and chlordiazepoxide in these two situations.ResultsOur results confirm that open-arm avoidance is a natural tendency and therefore that it is not learned during initial exposure to the maze. In addition, comparison of the two situations suggests that some of the open-arm entries during a forced confrontation with the maze are better interpreted as attempts to avoid the whole situation, rather than as indications of a low level of anxiety. Finally, the one-trial tolerance effect was partially reduced in the free-exposure situation.ConclusionsOur results contradict the hypothesis that there is acquisition of a phobic-like response to open arms during trial 1. Rather, they are discussed in line with the hypotheses by Rodgers and Shepherd (Psychopharmacology (Berl) 113:237–242, 1993) and Bertoglio and Carobrez (Behav Brain Res 108:197–203, 2000) concerning the acquisition of spatial information about the whole apparatus, leading on trial 2 to an unbalanced approach/avoidance conflict and to the inefficiency of anxiolytic drugs.

BALB/c mice are not so bad in the Morris water maze

We compared the learning performances of BALB/c mice subjected to the Morris water spatial task under two different lighting conditions. In the first one, the experimental room was lit by neon tubes (direct and bright illumination) and in the second one by a halogen lamp directed to the roof (diffuse illumination). The scores of BALB/c mice in the diffuse illumination condition clearly demonstrated that these mice could learn to escape to a hidden platform while they could not under direct illumination condition. Moreover, they were able to acquire the task by means of spatial cues. These results are interpreted in terms of a decrease of anxiety levels.

Early development of synchronized walking on the rotorod in rats: Effects of training and handling

There is considerable improvement of motor coordination on the rotorod during the first 3 weeks of development in rats. The purpose of the present study was to determine some factors implicated in this improvement. From days 15-22 of age, rats were: (1) extensively trained on the rotorod; (2) minimally trained on the rotorod; (3) handled daily but not trained on the rotorod; and (4) neither handled nor trained. All animals were tested on the rotorod on day 23, with separate groups of the naive rats also being tested on days, 19, 20, 21 or 22. Latencies before falling and the percentage of time spent walking in time to the movement of the rotating rod were recorded. There was a close correspondence between these two scores during ontogeny. The percentage of time spent walking was similar among extensively trained, minimally trained, and handled rats and significantly higher than that measured in rats tested only on 1 day. These results indicate that the emergence of this postural sensorimotor skill is more dependent on the maturation of sensorimotor brain region than on previous training on the apparatus.

EFFECTS OF HARMALINE ON ANXIETY-RELATED BEHAVIOR IN MICE

Harmaline (HA) is a beta-carboline commonly known to provoke motor alterations through activation of cells in the inferior olive. In addition, this pharmacological agent also induces cognitive disturbances such as motor and spatial learning impairments. In order to complete and extend these data, we examined the effects of this drug on state anxiety in mice, employing elevated plus maze test. We report here that lower doses of harmaline (5-10 mg/kg) have anxiogenic since higher doses (20 mg/kg) have anxiolytic-like properties. Overall pattern of our behavioral results provides evidence that harmaline also acts on emotional reactivity in mice by influencing their decision making when placed in an anxiogenic situation.

The positive effects of postnatal handling on defensive burying are more obvious in a situation that enlarges the potential coping responses.

A recent study reported few effects of postnatal handling in the defensive burying test. Since the importance of testing conditions has been emphasised in this paradigm, the lack of handling effects in this test could be attributed to the testing situation. Our experiment was carried out to test whether postnatal handling in DA/HAN strain rats have positive effects in two situations of the defensive burying test: a no-hide situation, in which avoidance of the probe was not possible, and a hide situation, in which animals were allowed to avoid the probe by sheltering in a hiding compartment. Our results showed no difference between control and handled rats defensive reactions in the no-hide situation. However, the general coping style of handled rats was different, mostly by a higher level of exploration of the apparatus and of the probe. In the hide situation, the time spent burying the probe was significantly lower in handled rats and they also spent less time in the hiding compartment. Those results, along with approach/avoidance behaviours directed towards the probe demonstrate that postnatal handling do have some positive effects in the defensive burying test. In addition, our results also point out that testing situations in which complex coping strategies are available are appropriate to test the effects of early stimulation such as handling.

The Effects of the Lurcher Mutation on Object Localization, T-Maze Discrimination, and Radial Arm Maze Tasks

The Lurcher mutation is characterized by degeneration of the cerebellar cortex and cerebellar ataxia. The mutants were compared to littermate controls of the same background strain in three spatial tasks: 1) left-right discrimination in a water-filled T-maze, a reference memory task requiring a win-stay strategy; 2) the radial arm maze, a working memory task requiring a win-shift strategy; 3) object localization, a reference memory task requiring the use of cognitive mapping. Lurcher mutants were impaired in the object localization and radial arm maze tasks but not in the left-right discrimination task. These results indicate that trial-independent tasks and reference memory tasks using cognitive mapping may be particularly vulnerable to cerebellar degeneration.

Balanced effect of PACAP and FasL on granule cell death during cerebellar development: a morphological, functional and behavioural characterization

J. Neurochem. (2010) 113, 329–340.