Biomedical subjects

Y Lamberty

Publications and source records attributed to Y Lamberty.

12 recordsLinked to original sources

PubMed2000

Absence of negative impact of levetiracetam on cognitive function and memory in normal and amygdala-kindled rats.

The effect of the new antiepileptic drug (AED) levetiracetam (LEV, Keppra) on cognitive function was studied in normal and amygdala-kindled rats by using the Morris water maze test. In addition, we investigated the effect of LEV on long-term potentiation (LTP) in rat hippocampal slices. Sodium valproate (VPA) was used as comparator in all studies. Clonazepam (CZP) and carbamazepine (CBZ) were used in normal rats. The results indicated that doses of LEV known to suppress motor seizures did not alter cognitive performance. In contrast, similar doses of the classic AEDs all decreased learning performance of the rats. Likewise, VPA did alter LTP but LEV was inactive. Amygdala-kindled rats were more sensitive than normal rats to the effects of VPA. These results suggest that LEV may be devoid of negative impact on cognition in epileptic patients.

Journal Article↗

PubMed1998

The mirror chamber test for testing anxiolytics: is there a mirror-induced stimulation?

A new murine model of anxiety, namely the mirror chamber test, is based on the assumption that, like many species, mice show approach-avoidance behavior when they are confronted by a mirror. It has been suggested that the mirror chamber is a specific and a quantitatively/qualitatively different measure of anxiety than that implicated in other behavioral models such as the elevated plus-maze and the head-dipping assays. The aim of the present study was to investigate whether there was indeed a specific mirror effect by replacing the mirrors in the chamber by either white or dark-gray tiles. Balb/c, DBA-derived, and C57 BL/6j mice were tested under these three experimental conditions. The results indicated that Balb/c and DBA-derived mice avoided the mirror, white and gray chambers similarly while C57 BL/6j mice entered more readily and spent more time in the gray chamber than in the mirrored or white chambers. Thus, depending on the strain of mouse studied, a brightness or a position effect in the chamber could explain the avoidance behavior observed. These results suggest that there is no need to invoke a specific mirror effect.

Animals↗

PubMed1996

Arm width and brightness modulation of spontaneous behaviour of two strains of mice tested in the elevated plus-maze.

Amongst the nonpharmacological variables that may influence spontaneous behaviour in the elevated plus-maze, at least two (namely, the width and brightness level of the maze arms) have not been evaluated for possible consequences on baseline activity. We therefore investigated the effect of width (5, 7, or 9 cm) and brightness level (grey vs. white) of the maze arms on the activity patterns of NMRI and C57/BL 10j mice in a plus-maze based on that described by Lister. Results indicated a clear strain difference in spontaneous behaviour in the open/closed arms with C57/BL mice making no visits on the open arms of the maze. In the NMRI strain, enlarging the arms resulted in significantly increased running in open arms but brightness level did not affect behavioural parameters. In the C57/BL mice, no significant behavioural changes were detected after increasing the arm width; however, the maze with a white floor significantly increased the latency to move and decreased ambulation. Finally, employing a maze with white closed arms and open grey arms resulted in ambulation by C57/BL mice into the open arms, a behaviour not normally observed in this strain using a uniformly bright maze. The results are discussed in terms of their putative effects in pharmacological testing.

Animals↗

PubMed1993

The aged mouse as a model of cognitive decline with special emphasis on studies in NMRI mice.

The use of the aged mouse as an integrated model of age-related cognitive decline is reviewed, with special emphasis on experiments covering the life span of NMRI mice, using different age-groups ranging from 3 through to 22 months. Age-related changes in the sensorimotor profile, spontaneous behaviour and performance in learning and memory tasks are considered. The data provide evidence for cognitive impairment and decreases in spontaneous activity and exploration from middle age onwards. Chronologically, this age depends on the longevity of the strain selected; in NMRI mice, middle age corresponds to 11-12 months. Complex learning tasks, such as the Morris water maze for spatial learning, appear to be the most sensitive to age-related changes, as are tests requiring prolonged retention of acquired information, for example, using passive avoidance. Cued and simple discrimination learning are only impaired in the oldest animals. Age-related changes in non-cognitive variables, including sensorimotor capacity, pain sensitivity, emotionality, or locomotor activity, do not account for the learning impairments, although deficits in visual acuity cannot be excluded in the very old animals. Detailed analysis of the individual data for middle aged and old mice, using discriminant and correlation studies highlight a marked heterogeneity between animals of any given chronological age. Furthermore, individual aged mice do not exhibit similar degrees of impairment across all the behavioural variables, showing that aging is not a uniform process. The possible relationship between age-related behavioural decline and neurochemical changes is an area as yet unexplored apart from a few isolated investigations, including a study on ChAT and AChE in NMRI mice. The studies in the NMRI mice illustrate the value of investigating the full age-range to detect an age group which shows cognitive decline dissociable from physical or emotional changes and which is representative of the population as a whole.

Aged↗

PubMed1993

Spatial processing and emotionality in aged NMRI mice: a multivariate analysis.

The goal of this study was to investigate possible relationships between different aspects of behavioural decline in aged (17 months) NMRI mice by a multivariate analysis. These mice presented defects in spatial processing both in place learning in a Morris-type water maze and in spontaneous alternation in a Y-maze, as well as showing changes in their behaviour in the elevated plus maze test of fear/anxiety and open-field ambulation. Data were first factor analysed and then correlated on the basis of variable factor scores. The results showed clearly that age-related behavioural changes were independent of each other except between open-field activity measured over 6 min and spatial learning indices in the Morris-type water maze, in that mice performing poorly in the latter were more active in the open field, and between the ratio open/total arms visited in the elevated plus maze task and locomotor activity during the first 2 min of the open-field test. It is proposed that the notion of an allocentric or locale system cannot be applied unitarily to both spatial learning and spontaneous alternation defects, and that activity levels in the aged mice are task dependent and reflect different underlying factors.

Aging↗

PubMed1992

Behavioural, biochemical and histological effects of AF64A following injection into the third ventricle of the mouse.

Behavioural, biochemical and histological effects were assessed following AF64A injected into the third ventricle of female NMRI mice. Doses from 3 to 7 nmol produced significant changes in behaviour, causing hyperactivity, reduced hole-board exploration, rotational behaviour in a symmetrical Y-maze corresponding to a loss of alternation, abnormal behaviour in a plus-maze task of fear/anxiety with markedly increased exploration of the open arms and finally deficits in passive avoidance responding and spatial orientation in a Morris-type water maze. In this latter test, a cue learning deficit was noted for the two highest doses only. No histological changes of consequence were observed up to 5 nmol. Beyond this dose, at 6 and particularly 7 nmol, necrosis of parts of the hippocampus and septum was apparent. ChAT and AChE activity were decreased in the hippocampus but not in the cortex although the decreases were smaller than generally reported for AF64A-treated rats. ChAT and AChE reductions correlated highly with hyperactivity in the open-field and to a lesser extent, with spatial learning deficits. Monoaminergic activity was also affected in the hippocampus, but not in the cortex, at 4 nmol and above. NE and particularly 5-HT and 5-HIAA levels were reduced although the rate of 5-HT turnover was unaltered. A highly significant correlation was obtained between 5-HT effects and the increased open arm exploration in the plus-maze task of fear/anxiety. The behavioural effects and biochemical changes lasted at least 8-9 weeks postop.

Acetylcholinesterase↗

PubMed1992

Age-related changes in spontaneous behavior and learning in NMRI mice from middle to old age.

Spontaneous behavior, sensorimotor reflexes and learning of 3-, 11-, 17- and 22-month-old virgin female NMRI mice were compared. Sensorimotor abilities decreased significantly from the age of 17 months in proportion to the muscular and equilibrium demand of the test. Open-field activity, hole board exploration as well as activity in the Y maze and plus maze decreased from the age of 11 months. However, in the open-field and Y maze, it was not possible to distinguish between 11-, 17- and 22-month-old mice, whereas in the plus maze, activity was drastically decreased in 17- and 22-month-old mice. In the plus maze, indices of fear-motivated behavior suggest a greater sensitivity to the situation in the age groups of 17 and 22 months. Spontaneous alternation also decreased from the age of 11 months, but at the age of 22 months, a rotational behavior emerged. Spatial learning was markedly impaired from middle age, i.e., 11 months, as indicated by longer latencies and absence of spatial bias in place learning. In cued learning, the 11- and 17-month groups eventually reached the level of the 3-month-old mice, while the 22-month age group remained impaired. Changes in swimming ability or speed did not appear to account for the swimming maze deficits. In contrast, a sensory or perceptual deficit cannot be excluded for the oldest mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1991

Simplifying environmental cues in a Morris-type water maze improves place learning in old NMRI mice.

Old virgin female NMRI mice aged 17 months were compared with mice aged 3 months for their spatial learning abilities in two versions of the Morris water maze. The first one was a simplified version with a salient configuration of cues comparable to a black/white discrimination and the second one was the classical version of the Morris test with many distal cues surrounding the maze. In the simplified version, old mice presented a slower rate of acquisition and a transient poorer retention compared to young mice. However, old mice achieved a final level of performance statistically comparable to their young counterparts as assessed by latencies to escape onto the concealed platform and by the spatial bias measured in probe trials at intervals during testing. When subsequently subjected to classical Morris maze learning, the same old animals showed marked learning deficits and were persistently impaired in their latencies to escape onto the platform. They presented no spatial bias for the location of the platform in the different probe trials. When the goal was cued at the end of the experiment, the performances of old mice rapidly improved, showing that motivation, motor disabilities, or fatigue and ability to use proximal cues cannot explain the place learning deficit. Our results were discussed in terms of cognitive versus sensory/perceptual disabilities in aged rats and mice.

Aging↗

PubMed1990

Age-related changes in spontaneous behavior and learning in NMRI mice from maturity to middle age.

Spontaneous behavior and learning and memory of 3-, 6-, 9- and 12-month-old virgin female NMRI mice were compared. Open field activity and spontaneous alternation in a Y-maze decreased in an age-related manner, reaching a statistical level of significance for the groups aged 9 and 12 months. Spatial learning was highly impaired in 9-and 12-month-old mice in the place version of a Morris-type water maze but not in the cued version of this task. Changes in motor activity, swimming ability or speed did not appear to account for these deficits. In a one-trial passive avoidance, performance was more variable, although a deficit in the oldest age group was clearly evident using a cutoff time of 120 sec. The passive avoidance was not attributable to reduced shock sensitivity. Together, these results suggest that the onset of aging in NMRI mice occurs at the age of 9 and particularly 12 months. NMRI mice of this age could, therefore, represent a viable animal model for the study of cognitive impairments in aging.

Aging↗

PubMed1988

Investigation into sex-related differences in locomotor activity, place learning and passive avoidance responding in NMRI mice.

Learning abilities of young adult (5-6 weeks) male and female NMRI mice were compared in two tasks involving cognitive functions, namely spatial learning in a water maze and passive avoidance responding. Locomotor activity was also monitored as a putative bias for the results obtained in these learning tests. No sex-related difference was observed either in avoidance responding or in spatial learning using a procedure with the same point of departure throughout testing in the water maze. However, in this test, using a procedure with 3 different points of departure in randomized order day after day, female mice performed better than male mice. The difference was statistically significant on the last acquisition day but was not sustained during a retention trial 72 hr later. Since no sex differences in locomotor activity were observed, the learning effects cannot be attributed to a difference in general activity level.

Animals↗

PubMed1987

Scopolamine disrupts visual reversal without affecting the first discrimination.

The effect of scopolamine (0.5 mg/kg) was determined in a brightness discrimination test (Y maze) motivated by electrical shocks (escape avoidance). Male adult Sprague Dawley rats were used. Results show that scopolamine impairs significantly the visual reversal without affecting the first brightness discrimination. The qualitative analysis reveals that the anticholinergic drug-induced deficit involves both perseveration, i.e. failure to suppress inappropriate response, and a tendency to adopt a position habit. A parallelism with hippocampal and frontal lobe damage symptoms is discussed and an interpretation in terms of disinhibition and incapacity to solve a more difficult problem is proposed.

Animals↗

PubMedDate not supplied

Cholinergic modulation of spatial learning in mice in a Morris-type water maze.

Injection of the centrally active muscarinic antagonist scopolamine i.p. 20 min pre-test at 3 mg/kg but not at 1 mg/kg, impaired spatial learning of a Morris-type water maze adapted for mice. Both doses caused hyperactivity. D-amphetamine (3 mg/kg, i.p.), which also caused hyperactivity, did not impair spatial learning nor did methylscopolamine (3 mg/kg, i.p.). In a cued version of the water maze, apart from a temporary disturbance on day 1, scopolamine (3 mg/kg) and control groups behaved similarly, indicating that scopolamine-induced place learning deficits are not due to changes in swimming ability, motivation or ability to use proximal cues. Physostigmine (0.1 and 0.2 mg/kg, i.p.) and oxotremorine (0.02 mg/kg but not 0.01 mg/kg, i.p.) antagonized the deficits in the swimming maze. Neither drug affected the scopolamine hyperactivity despite causing hypoactivity per se. In contrast, the peripherally acting cholinergic drug neostigmine was inactive against scopolamine in either test at 0.1 mg/kg. THA (2-8 mg/kg, i.p.), RS86 (0.25-1 mg/kg, i.p.) and nicotine (1 and 3 mg/kg, i.p.) were also unable to antagonize the scopolamine effect. These studies show that scopolamine disrupts acquisition of spatial rather than cued learning in mice in a Morris-type water maze and that this effect appears to be mediated centrally and can be dissociated from drug-induced hyperactivity. Moreover, this deficit can be reversed with certain cholinergic agents.

Animals↗