Charles Cohen-Salmon - Academia.edu (original) (raw)

Papers by Charles Cohen-Salmon

Behavioural Brain Research, 2004

Chronic low grade stress predispose to psychopathological disorders. We consistently showed that ... more Chronic low grade stress predispose to psychopathological disorders. We consistently showed that chronic ultra-mild stress (CUMS) applied to B6D2F1 female mice induced behavioral disinhibition in several conflict exploration models. Insufficient reactivity to conflicts may be maladaptive and lead to inappropriate appreciation of potential risks and impaired ability to cope with those. Therefore, the purpose of the study was to assess the effect of a CUMS procedure on the behavior of mice in a motor risk situation based on multisensory conflict. Following three weeks exposure to various mild stressors, stressed and control B6D2F1 mice were tested on the rotating beam to determine how CUMS exposure affected balance control, posture stability and locomotor performance in response to a sensory-motor challenge. Detailed behavioral analysis included several parameters, both postural (height of the trunk, tail angle, number of imbalances, falls and head movements) and kinetic (mean velocity on the beam, distance covered with large and small movements, plus time spent in no-motion episodes). Comparisons between control and stressed mice showed that CUMS exposure increased mean velocity and improved locomotor performance in the learning task. In addition, sensitivity to sensory conflict seemed to be reduced in stressed mice, which displayed fewer behavioral adjustments to the increasing difficulty of the test compared to control mice. The results are discussed in terms of the possible influence of disturbances in behavioral and attentional inhibitory processes following CUMS exposure. Whether longer periods of CUMS exposure would shift the performance on the RTB from improvement to deterioration remain to be established.

Psychiatry Research, 2005

Fluctuations in steroid hormones (glucocorticoids and estradiol) levels during pregnancy and afte... more Fluctuations in steroid hormones (glucocorticoids and estradiol) levels during pregnancy and after delivery are thought to contribute to the etiology of postpartum depression. Such changes may be exacerbated by stressful events, which constitute a predisposing factor for postpartum mood disorders. In the present study, blood hormonal variations associated with prepartum Chronic Ultramild Stress (CUMS) exposure were assessed at two times (15th day of pregnancy and 3rd day postpartum) in mice stressed from day 1 of pregnancy to termination of pregnancy. Litter weight and litter size were determined in both groups whereas the duration of pregnancy was determined in the 3-day postpartum group. CUMS increased estradiol and corticosterone levels during pregnancy, but such effects were no longer observed in the postpartum period, where cortisol levels were decreased in control and stressed mice and estradiol levels were reduced in previously stressed mothers. No effects of the CUMS procedure were observed on gestational parameters. Given the link between hormonal variations during pregnancy and subsequent postpartum depression, these results suggest that CUMS applied to gestating female may provide a useful model for the study of the mechanisms of stress, which may lead to postpartum mood disorders. D

Physiology & Behavior, 1987

An improvement in two variables of a retrieving test has been shown in eight inbred strains of mi... more An improvement in two variables of a retrieving test has been shown in eight inbred strains of mice following the second parturition. To test the possible contribution of presence at birth and/or caregiving to a cohabitation effect, retrieval behavior was measured in four groups of XLII inbred mice: one group of biparas, and three groups of primiparas; one without any previous maternal experience, one previously exposed to parturition and caregiving by an alien female, and one exposed to a female with her newborn litter. The two variables do not discriminate between the groups in the same way. The scores on one variable (first retrieval latency) fit into an increasingly complex hierarchy of cohabitational environment with parturient females. The second variable (move away from the pups) discriminates between those primiparas who had a cohabitational experience including both birth and caregiving and those that did not. Dissimilarities between the actions of these two variables are discussed in the light of genetic and ethological mechanisms.

Brain Research Protocols, 2004

The implication of integrated functional sensory relations of the body to space in anxiety disord... more The implication of integrated functional sensory relations of the body to space in anxiety disorders is a very important issue which encourages the development of animal models, in particular, for pharmacological perspectives and for the functional assessment of the deficits induced by genetic manipulation in the mouse or the rat. A new experimental device is presented here: It is comprised of a rotating tunnel and a rotating-beam controlled by computer which can be used for multiple visuo-idiothetic and kinesthetic sensory conflict situations during active locomotor behaviour by mice. The system is linked to a digital video system, Video-Track trade mark, designed to track and record the movements of the animals. Anxious BALB/cByJ mice were compared to non-anxious C57BL/6J mice and were seen to display highly disturbed locomotor behaviour in a sensory conflict situation. The model highlights the advantages of video-digital analysis for animal behavioural sciences.

Behavioural Brain Research, 2004

Chronic low grade stress predispose to psychopathological disorders. We consistently showed that ... more Chronic low grade stress predispose to psychopathological disorders. We consistently showed that chronic ultra-mild stress (CUMS) applied to B6D2F1 female mice induced behavioral disinhibition in several conflict exploration models. Insufficient reactivity to conflicts may be maladaptive and lead to inappropriate appreciation of potential risks and impaired ability to cope with those. Therefore, the purpose of the study was to assess the effect of a CUMS procedure on the behavior of mice in a motor risk situation based on multisensory conflict. Following three weeks exposure to various mild stressors, stressed and control B6D2F1 mice were tested on the rotating beam to determine how CUMS exposure affected balance control, posture stability and locomotor performance in response to a sensory-motor challenge. Detailed behavioral analysis included several parameters, both postural (height of the trunk, tail angle, number of imbalances, falls and head movements) and kinetic (mean velocity on the beam, distance covered with large and small movements, plus time spent in no-motion episodes). Comparisons between control and stressed mice showed that CUMS exposure increased mean velocity and improved locomotor performance in the learning task. In addition, sensitivity to sensory conflict seemed to be reduced in stressed mice, which displayed fewer behavioral adjustments to the increasing difficulty of the test compared to control mice. The results are discussed in terms of the possible influence of disturbances in behavioral and attentional inhibitory processes following CUMS exposure. Whether longer periods of CUMS exposure would shift the performance on the RTB from improvement to deterioration remain to be established. (C. Cohen-Salmon).

Life sciences, 1995

Female mice of the inbred strains C57BL/6J, BALB/cJ and DBA/2J were used to determine the possibl... more Female mice of the inbred strains C57BL/6J, BALB/cJ and DBA/2J were used to determine the possible existence of a genetically-based differential susceptibility to the effects of treatment with an extract of Ginkgo biloba (EGb 761). Timm's silver-sulphide staining method was used to visualize and determine changes in the areas of the hippocampal structures of aged subjects, and more specifically on the projection fields of the mossy fibers which appear to decrease as a function of ageing. Experiments were begun when the animals were 15 months old. Treated animals received EGb 761 (50 mg/kg/day, p.o.) for 7 months in their drinking water. Inter-strain differences existed for the areas of the whole regio inferior, stratum pyramidale, stratum lacunosum moleculare and hilus (CA4) and for the projection field of intra- and infrapyramidal mossy fibers (iipMF) in the CA3 region of the hippocampus. Chronic treatment with EGb 761 significantly increased the projection field of iipMF and s...

European Psychiatry, 2006

According to human observations of a syndrome of physical activity dependence and its consequence... more According to human observations of a syndrome of physical activity dependence and its consequences, we tried to examine if running activity in a free activity paradigm, where rats had a free access to activity wheel, may present a valuable animal model for physical activity dependence and most generally to behavioral dependence. The pertinence of reactivity to novelty, a well-known pharmacological dependence predictor was also tested. Given the close linkage observed in human between physical activity and drugs use and abuse, the influence of free activity in activity wheels on reactivity to amphetamine injection and reactivity to novelty were also assessed. It appeared that (1) free access to wheel may be used as a valuable model for physical activity addiction, (2) two populations differing in activity amount also differed in dependence to wheel-running. (3) Reactivity to novelty did not appeared as a predictive factor for physical activity dependence (4) activity modified novelty reactivity and (5) subjects who exhibited a high appetence to wheel-running, presented a strong reactivity to amphetamine. These results propose a model of dependency on physical activity without any pharmacological intervention, and demonstrate the existence of individual differences in the development of this addiction. In addition, these data highlight the development of a likely vulnerability to pharmacological addiction after intense and sustained physical activity, as also described in man. This model could therefore prove pertinent for studying behavioral dependencies and the underlying neurobiological mechanisms. These results may influence the way psychiatrists view behavioral dependencies and phenomena such as doping in sport or addiction to sport itself.

Brain Research Bulletin, 2002

Because pharmacological and genetic data supported the idea that serotonin receptors of the 5-HT ... more Because pharmacological and genetic data supported the idea that serotonin receptors of the 5-HT 1B type can play a modulatory role in alcohol consumption in both human and rodents, the 5-HT 1B receptor gene is considered as a candidate gene for alcohol dependence. However, contradictory results have been reported as a positive association between alcohol dependence, and either the 861C or the 861G allele of the G861C polymorphism of the 5-HT 1B receptor gene can be found in the literature. Further investigations in a population of 136 male alcoholics compared with 72 male control subjects demonstrated that none of these alleles was actually associated with alcohol dependence. In addition, in contrast with previous results of the literature, ethanol intake under free choice conditions (i.e., ethanol solution vs. water) was found to be similar in 5-HT 1B ؊/؊ knock mice and paired wild-type controls. The 5-HT 1B receptor gene may thus not be a key component in the genetic background underlying alcohol dependence in human and alcohol preference in rodents, although these results should be considered as preliminary according to the small size of our sample.

Alcohol and Alcoholism, 2003

Experimental neurology, 2002

The loss of dopaminergic neurons in Parkinson's disease is associated with a glial reaction a... more The loss of dopaminergic neurons in Parkinson's disease is associated with a glial reaction and the overproduction of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha). TNF-alpha acts via two different receptors, TNFR1 and TNFR2, and is believed to have both a neuroprotective and a deleterious role for neurons. In order to analyze the putative role of TNF-alpha in parkinsonism, we compared the effect of the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice lacking TNFR1, TNFR2, or both receptors and in wild-type littermates. We show that MPTP does not affect spontaneous activity or anxiety in any of the groups and that it reduces motor activity on a rotarod in double knock out mice but not in mice lacking only one receptor. Postmortem analysis revealed no differences in the number of nigral dopaminergic neurons whatever the group. In contrast, striatal dopamine level was slightly decreased in double knock-out mice and more redu...

Physiology & Behavior, 2000

Few studies have been devoted to the interaction between age and stress. However, in view of the ... more Few studies have been devoted to the interaction between age and stress. However, in view of the age-related changes in various components of the stress responses, the effects of stress may not be constant with age. In this study, we used a dimensional approach to compare open-field behaviour of B6D2F1 female mice, aged 5-6, 11-12, 17-18 and 23-24 months, exposed to a chronic ultramild stress (CUMS) procedure, solely based on nonnociceptive socioenvironmental stressors. Three behavioural dimensions emerged from the principal-component analysis; these were labelled as motor reactivity, exploratory activity, and emotional reactivity. Despite a major effect of age on the three dimensions, we could not conclude that CUMS had any influence as a function the age of the subjects. At all ages, CUMS increased motor activity and had no clear-cut effect on emotional reactivity and exploratory activity. The results are discussed in terms of the influence of the nature of the stressors on behavioural responses to novelty.

Translational Stroke Research, 2012

Ph: 00 33 (0)1 40 03 19 76 Fax: 0 33 (0)1 40 03 19 95 Abstract: 259 words Body: 6587 words Tables... more Ph: 00 33 (0)1 40 03 19 76 Fax: 0 33 (0)1 40 03 19 95 Abstract: 259 words Body: 6587 words Tables: 1 Figures: 4 Abstract

Journal of Neuroscience, 2004

In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the ... more In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the density of cytosolic GR binding sites in the hippocampus, whereas, in the DRN, GR mRNA levels tended to increase. In contrast, in stressed GR-i mice, both GR mRNA levels and the density of GR binding sites were significantly increased in the hippocampus, cerebral cortex, and DRN. Electrophysiological recordings in brainstem slices and [␥-35 S]GTP-S binding measurements to assess 5-HT 1A receptor functioning showed that CMS exposure produced a desensitization of DRN 5-HT 1A autoreceptors in WT, but not in GR-i, mice. In addition, CMS was found to facilitate choice behavior of WT, but not GR-i, mice in a decision-making task derived from an alternation paradigm. These results demonstrate that impaired GR functioning affects normal adaptive responses of the HPA axis and 5-HT system to CMS and alters stress-related consequences on decision-making behaviors.

Journal of Neuroscience, 2007

Cerebral palsy remains a public health priority. Recognition of factors of susceptibility to peri... more Cerebral palsy remains a public health priority. Recognition of factors of susceptibility to perinatal brain lesions is key for the prevention of cerebral palsy. In most cases, the pathophysiology of these lesions is thought to involve prior exposure to predisposing factors that make the developing brain more vulnerable to perinatal events. The present study tested the hypothesis that exposure to chronic minimal stress throughout gestation would sensitize the offspring to neonatal excitotoxic brain lesions, which mimic lesions observed in cerebral palsy. Pregnant mice were exposed to chronic, ultramild stress, applied throughout gestation. Neonatal brain lesions were induced by intracerebral injection of glutamate analogs. Excitotoxic lesions were significantly worsened in pups exposed to gestational stress. Stress induced a significant rise of circulating corticosterone levels both in pregnant mothers and in newborn pups. The deleterious effects of stress on excitotoxicity were totally suppressed in mice with reduced levels of glucocorticoid receptors. Stress induced a significant increase of neopallial NMDA binding sites in the offspring. At adulthood, animals exposed to stress and neonatal excitotoxic challenge showed a significant impairment in the Morris water maze test when compared with animals exposed to the excitotoxic challenge but not the gestational stress. These findings suggest that stress during gestation, which may mimic low-level stress in human pregnancy, could be a novel risk factor for cerebral palsy.

PLoS ONE, 2009

In synucleinopathies, including Parkinson's disease, partially ubiquitylated a-synuclein species ... more In synucleinopathies, including Parkinson's disease, partially ubiquitylated a-synuclein species phosphorylated on serine 129 (P S129 -a-synuclein) accumulate abnormally. Parkin, an ubiquitin-protein ligase that is dysfunctional in autosomal recessive parkinsonism, protects against a-synuclein-mediated toxicity in various models. We analyzed the effects of Parkin deficiency in a mouse model of synucleinopathy to explore the possibility that Parkin and a-synuclein act in the same biochemical pathway. Whether or not Parkin was present, these mice developed an age-dependent neurodegenerative disorder preceded by a progressive decline in performance in tasks predictive of sensorimotor dysfunction. The symptoms were accompanied by the deposition of P S129 -a-synuclein but not P S87 -a-synuclein in neuronal cell bodies and neuritic processes throughout the brainstem and the spinal cord; activation of caspase 9 was observed in 5% of the P S129 -asynuclein-positive neurons. As in Lewy bodies, ubiquitin-immunoreactivity, albeit less abundant, was invariably co-localized with P S129 -a-synuclein. During late disease stages, the disease-specific neuropathological features revealed by ubiquitinand P S129 -a-synuclein-specific antibodies were similar in mice with or without Parkin. However, the proportion of P S129 -asynuclein-immunoreactive neuronal cell bodies and neurites co-stained for ubiquitin was lower in the absence than in the presence of Parkin, suggesting less advanced synucleinopathy. Moreover, sensorimotor impairment and manifestation of the neurodegenerative phenotype due to overproduction of human a-synuclein were significantly delayed in Parkindeficient mice. These findings raise the possibility that effective compensatory mechanisms modulate the phenotypic expression of disease in parkin-related parkinsonism. Citation: Fournier M, Vitte J, Garrigue J, Langui D, Dullin J-P, et al. (2009) Parkin Deficiency Delays Motor Decline and Disease Manifestation in a Mouse Model of Synucleinopathy. PLoS ONE 4(8): e6629.

Physiology & Behavior, 1985

Physiology & Behavior, 1989

Exploratory, locomotor and ambulatory activities were measured in nine independent groups of thre... more Exploratory, locomotor and ambulatory activities were measured in nine independent groups of three inbred strains of mice (BALB/cBy, C57BL/6J and DBA/2J), at three different ages (150 days, 400 days and 750 days). The results show that for two of the three variables, the age-related changes present different patterns as a function of strain. The genetic and/or environmental correlates of the reactivity to aging may thus depend on the behavioral trait under study.

Physiology & Behavior, 1983

CARLIER, M., P. ROUBERTOUX AND CH. COHEN-SALMON. Early development in mice: 1. Genotype and postn... more CARLIER, M., P. ROUBERTOUX AND CH. COHEN-SALMON. Early development in mice: 1. Genotype and postnatal maternal effects. PHYSIOL BEHAV 30(6) 837-844, 1983.--The co-actions of genetic effects and the post-natal maternal rearing environment on the development of weight, 9 reflex responses, and survival have been tested by the cross-fostering method in two inbred mice strains---CBA/H and NZB. Pups of the two strains were not treated differentially by the mothers and experimental handling did not systematically affect pup development. Comparisons of unfostered, infostered, and cross-fostered pups show (1) in 16 cases out of 34, reflex development was affected by the pup strain, and in 10 cases out of 34 by the foster mother strain; (2) survival is only affected by the pup strain; (3) weight development is affected by strain of both the pup and the mother as well as their interactions. The adopted pups' scores were situated outside the range of the two non-adopted groups for certain reflexes as well as for weight. Two non-exclusive hypotheses are proposed: the mother strain can affect pup development (1) either through differences in stimulation provided by the mothers (2) or through differences in milk composition.

Behavioural Brain Research, 2004

Chronic low grade stress predispose to psychopathological disorders. We consistently showed that ... more Chronic low grade stress predispose to psychopathological disorders. We consistently showed that chronic ultra-mild stress (CUMS) applied to B6D2F1 female mice induced behavioral disinhibition in several conflict exploration models. Insufficient reactivity to conflicts may be maladaptive and lead to inappropriate appreciation of potential risks and impaired ability to cope with those. Therefore, the purpose of the study was to assess the effect of a CUMS procedure on the behavior of mice in a motor risk situation based on multisensory conflict. Following three weeks exposure to various mild stressors, stressed and control B6D2F1 mice were tested on the rotating beam to determine how CUMS exposure affected balance control, posture stability and locomotor performance in response to a sensory-motor challenge. Detailed behavioral analysis included several parameters, both postural (height of the trunk, tail angle, number of imbalances, falls and head movements) and kinetic (mean velocity on the beam, distance covered with large and small movements, plus time spent in no-motion episodes). Comparisons between control and stressed mice showed that CUMS exposure increased mean velocity and improved locomotor performance in the learning task. In addition, sensitivity to sensory conflict seemed to be reduced in stressed mice, which displayed fewer behavioral adjustments to the increasing difficulty of the test compared to control mice. The results are discussed in terms of the possible influence of disturbances in behavioral and attentional inhibitory processes following CUMS exposure. Whether longer periods of CUMS exposure would shift the performance on the RTB from improvement to deterioration remain to be established.

Psychiatry Research, 2005

Fluctuations in steroid hormones (glucocorticoids and estradiol) levels during pregnancy and afte... more Fluctuations in steroid hormones (glucocorticoids and estradiol) levels during pregnancy and after delivery are thought to contribute to the etiology of postpartum depression. Such changes may be exacerbated by stressful events, which constitute a predisposing factor for postpartum mood disorders. In the present study, blood hormonal variations associated with prepartum Chronic Ultramild Stress (CUMS) exposure were assessed at two times (15th day of pregnancy and 3rd day postpartum) in mice stressed from day 1 of pregnancy to termination of pregnancy. Litter weight and litter size were determined in both groups whereas the duration of pregnancy was determined in the 3-day postpartum group. CUMS increased estradiol and corticosterone levels during pregnancy, but such effects were no longer observed in the postpartum period, where cortisol levels were decreased in control and stressed mice and estradiol levels were reduced in previously stressed mothers. No effects of the CUMS procedure were observed on gestational parameters. Given the link between hormonal variations during pregnancy and subsequent postpartum depression, these results suggest that CUMS applied to gestating female may provide a useful model for the study of the mechanisms of stress, which may lead to postpartum mood disorders. D

Physiology & Behavior, 1987

An improvement in two variables of a retrieving test has been shown in eight inbred strains of mi... more An improvement in two variables of a retrieving test has been shown in eight inbred strains of mice following the second parturition. To test the possible contribution of presence at birth and/or caregiving to a cohabitation effect, retrieval behavior was measured in four groups of XLII inbred mice: one group of biparas, and three groups of primiparas; one without any previous maternal experience, one previously exposed to parturition and caregiving by an alien female, and one exposed to a female with her newborn litter. The two variables do not discriminate between the groups in the same way. The scores on one variable (first retrieval latency) fit into an increasingly complex hierarchy of cohabitational environment with parturient females. The second variable (move away from the pups) discriminates between those primiparas who had a cohabitational experience including both birth and caregiving and those that did not. Dissimilarities between the actions of these two variables are discussed in the light of genetic and ethological mechanisms.

Brain Research Protocols, 2004

The implication of integrated functional sensory relations of the body to space in anxiety disord... more The implication of integrated functional sensory relations of the body to space in anxiety disorders is a very important issue which encourages the development of animal models, in particular, for pharmacological perspectives and for the functional assessment of the deficits induced by genetic manipulation in the mouse or the rat. A new experimental device is presented here: It is comprised of a rotating tunnel and a rotating-beam controlled by computer which can be used for multiple visuo-idiothetic and kinesthetic sensory conflict situations during active locomotor behaviour by mice. The system is linked to a digital video system, Video-Track trade mark, designed to track and record the movements of the animals. Anxious BALB/cByJ mice were compared to non-anxious C57BL/6J mice and were seen to display highly disturbed locomotor behaviour in a sensory conflict situation. The model highlights the advantages of video-digital analysis for animal behavioural sciences.

Behavioural Brain Research, 2004

Chronic low grade stress predispose to psychopathological disorders. We consistently showed that ... more Chronic low grade stress predispose to psychopathological disorders. We consistently showed that chronic ultra-mild stress (CUMS) applied to B6D2F1 female mice induced behavioral disinhibition in several conflict exploration models. Insufficient reactivity to conflicts may be maladaptive and lead to inappropriate appreciation of potential risks and impaired ability to cope with those. Therefore, the purpose of the study was to assess the effect of a CUMS procedure on the behavior of mice in a motor risk situation based on multisensory conflict. Following three weeks exposure to various mild stressors, stressed and control B6D2F1 mice were tested on the rotating beam to determine how CUMS exposure affected balance control, posture stability and locomotor performance in response to a sensory-motor challenge. Detailed behavioral analysis included several parameters, both postural (height of the trunk, tail angle, number of imbalances, falls and head movements) and kinetic (mean velocity on the beam, distance covered with large and small movements, plus time spent in no-motion episodes). Comparisons between control and stressed mice showed that CUMS exposure increased mean velocity and improved locomotor performance in the learning task. In addition, sensitivity to sensory conflict seemed to be reduced in stressed mice, which displayed fewer behavioral adjustments to the increasing difficulty of the test compared to control mice. The results are discussed in terms of the possible influence of disturbances in behavioral and attentional inhibitory processes following CUMS exposure. Whether longer periods of CUMS exposure would shift the performance on the RTB from improvement to deterioration remain to be established. (C. Cohen-Salmon).

Life sciences, 1995

Female mice of the inbred strains C57BL/6J, BALB/cJ and DBA/2J were used to determine the possibl... more Female mice of the inbred strains C57BL/6J, BALB/cJ and DBA/2J were used to determine the possible existence of a genetically-based differential susceptibility to the effects of treatment with an extract of Ginkgo biloba (EGb 761). Timm's silver-sulphide staining method was used to visualize and determine changes in the areas of the hippocampal structures of aged subjects, and more specifically on the projection fields of the mossy fibers which appear to decrease as a function of ageing. Experiments were begun when the animals were 15 months old. Treated animals received EGb 761 (50 mg/kg/day, p.o.) for 7 months in their drinking water. Inter-strain differences existed for the areas of the whole regio inferior, stratum pyramidale, stratum lacunosum moleculare and hilus (CA4) and for the projection field of intra- and infrapyramidal mossy fibers (iipMF) in the CA3 region of the hippocampus. Chronic treatment with EGb 761 significantly increased the projection field of iipMF and s...

European Psychiatry, 2006

According to human observations of a syndrome of physical activity dependence and its consequence... more According to human observations of a syndrome of physical activity dependence and its consequences, we tried to examine if running activity in a free activity paradigm, where rats had a free access to activity wheel, may present a valuable animal model for physical activity dependence and most generally to behavioral dependence. The pertinence of reactivity to novelty, a well-known pharmacological dependence predictor was also tested. Given the close linkage observed in human between physical activity and drugs use and abuse, the influence of free activity in activity wheels on reactivity to amphetamine injection and reactivity to novelty were also assessed. It appeared that (1) free access to wheel may be used as a valuable model for physical activity addiction, (2) two populations differing in activity amount also differed in dependence to wheel-running. (3) Reactivity to novelty did not appeared as a predictive factor for physical activity dependence (4) activity modified novelty reactivity and (5) subjects who exhibited a high appetence to wheel-running, presented a strong reactivity to amphetamine. These results propose a model of dependency on physical activity without any pharmacological intervention, and demonstrate the existence of individual differences in the development of this addiction. In addition, these data highlight the development of a likely vulnerability to pharmacological addiction after intense and sustained physical activity, as also described in man. This model could therefore prove pertinent for studying behavioral dependencies and the underlying neurobiological mechanisms. These results may influence the way psychiatrists view behavioral dependencies and phenomena such as doping in sport or addiction to sport itself.

Brain Research Bulletin, 2002

Because pharmacological and genetic data supported the idea that serotonin receptors of the 5-HT ... more Because pharmacological and genetic data supported the idea that serotonin receptors of the 5-HT 1B type can play a modulatory role in alcohol consumption in both human and rodents, the 5-HT 1B receptor gene is considered as a candidate gene for alcohol dependence. However, contradictory results have been reported as a positive association between alcohol dependence, and either the 861C or the 861G allele of the G861C polymorphism of the 5-HT 1B receptor gene can be found in the literature. Further investigations in a population of 136 male alcoholics compared with 72 male control subjects demonstrated that none of these alleles was actually associated with alcohol dependence. In addition, in contrast with previous results of the literature, ethanol intake under free choice conditions (i.e., ethanol solution vs. water) was found to be similar in 5-HT 1B ؊/؊ knock mice and paired wild-type controls. The 5-HT 1B receptor gene may thus not be a key component in the genetic background underlying alcohol dependence in human and alcohol preference in rodents, although these results should be considered as preliminary according to the small size of our sample.

Alcohol and Alcoholism, 2003

Experimental neurology, 2002

The loss of dopaminergic neurons in Parkinson's disease is associated with a glial reaction a... more The loss of dopaminergic neurons in Parkinson's disease is associated with a glial reaction and the overproduction of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha). TNF-alpha acts via two different receptors, TNFR1 and TNFR2, and is believed to have both a neuroprotective and a deleterious role for neurons. In order to analyze the putative role of TNF-alpha in parkinsonism, we compared the effect of the parkinsonian drug 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice lacking TNFR1, TNFR2, or both receptors and in wild-type littermates. We show that MPTP does not affect spontaneous activity or anxiety in any of the groups and that it reduces motor activity on a rotarod in double knock out mice but not in mice lacking only one receptor. Postmortem analysis revealed no differences in the number of nigral dopaminergic neurons whatever the group. In contrast, striatal dopamine level was slightly decreased in double knock-out mice and more redu...

Physiology & Behavior, 2000

Few studies have been devoted to the interaction between age and stress. However, in view of the ... more Few studies have been devoted to the interaction between age and stress. However, in view of the age-related changes in various components of the stress responses, the effects of stress may not be constant with age. In this study, we used a dimensional approach to compare open-field behaviour of B6D2F1 female mice, aged 5-6, 11-12, 17-18 and 23-24 months, exposed to a chronic ultramild stress (CUMS) procedure, solely based on nonnociceptive socioenvironmental stressors. Three behavioural dimensions emerged from the principal-component analysis; these were labelled as motor reactivity, exploratory activity, and emotional reactivity. Despite a major effect of age on the three dimensions, we could not conclude that CUMS had any influence as a function the age of the subjects. At all ages, CUMS increased motor activity and had no clear-cut effect on emotional reactivity and exploratory activity. The results are discussed in terms of the influence of the nature of the stressors on behavioural responses to novelty.

Translational Stroke Research, 2012

Ph: 00 33 (0)1 40 03 19 76 Fax: 0 33 (0)1 40 03 19 95 Abstract: 259 words Body: 6587 words Tables... more Ph: 00 33 (0)1 40 03 19 76 Fax: 0 33 (0)1 40 03 19 95 Abstract: 259 words Body: 6587 words Tables: 1 Figures: 4 Abstract

Journal of Neuroscience, 2004

In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the ... more In the latter animals, CMS exposure caused a significant decrease in both GR mRNA levels and the density of cytosolic GR binding sites in the hippocampus, whereas, in the DRN, GR mRNA levels tended to increase. In contrast, in stressed GR-i mice, both GR mRNA levels and the density of GR binding sites were significantly increased in the hippocampus, cerebral cortex, and DRN. Electrophysiological recordings in brainstem slices and [␥-35 S]GTP-S binding measurements to assess 5-HT 1A receptor functioning showed that CMS exposure produced a desensitization of DRN 5-HT 1A autoreceptors in WT, but not in GR-i, mice. In addition, CMS was found to facilitate choice behavior of WT, but not GR-i, mice in a decision-making task derived from an alternation paradigm. These results demonstrate that impaired GR functioning affects normal adaptive responses of the HPA axis and 5-HT system to CMS and alters stress-related consequences on decision-making behaviors.

Journal of Neuroscience, 2007

Cerebral palsy remains a public health priority. Recognition of factors of susceptibility to peri... more Cerebral palsy remains a public health priority. Recognition of factors of susceptibility to perinatal brain lesions is key for the prevention of cerebral palsy. In most cases, the pathophysiology of these lesions is thought to involve prior exposure to predisposing factors that make the developing brain more vulnerable to perinatal events. The present study tested the hypothesis that exposure to chronic minimal stress throughout gestation would sensitize the offspring to neonatal excitotoxic brain lesions, which mimic lesions observed in cerebral palsy. Pregnant mice were exposed to chronic, ultramild stress, applied throughout gestation. Neonatal brain lesions were induced by intracerebral injection of glutamate analogs. Excitotoxic lesions were significantly worsened in pups exposed to gestational stress. Stress induced a significant rise of circulating corticosterone levels both in pregnant mothers and in newborn pups. The deleterious effects of stress on excitotoxicity were totally suppressed in mice with reduced levels of glucocorticoid receptors. Stress induced a significant increase of neopallial NMDA binding sites in the offspring. At adulthood, animals exposed to stress and neonatal excitotoxic challenge showed a significant impairment in the Morris water maze test when compared with animals exposed to the excitotoxic challenge but not the gestational stress. These findings suggest that stress during gestation, which may mimic low-level stress in human pregnancy, could be a novel risk factor for cerebral palsy.

PLoS ONE, 2009

In synucleinopathies, including Parkinson's disease, partially ubiquitylated a-synuclein species ... more In synucleinopathies, including Parkinson's disease, partially ubiquitylated a-synuclein species phosphorylated on serine 129 (P S129 -a-synuclein) accumulate abnormally. Parkin, an ubiquitin-protein ligase that is dysfunctional in autosomal recessive parkinsonism, protects against a-synuclein-mediated toxicity in various models. We analyzed the effects of Parkin deficiency in a mouse model of synucleinopathy to explore the possibility that Parkin and a-synuclein act in the same biochemical pathway. Whether or not Parkin was present, these mice developed an age-dependent neurodegenerative disorder preceded by a progressive decline in performance in tasks predictive of sensorimotor dysfunction. The symptoms were accompanied by the deposition of P S129 -a-synuclein but not P S87 -a-synuclein in neuronal cell bodies and neuritic processes throughout the brainstem and the spinal cord; activation of caspase 9 was observed in 5% of the P S129 -asynuclein-positive neurons. As in Lewy bodies, ubiquitin-immunoreactivity, albeit less abundant, was invariably co-localized with P S129 -a-synuclein. During late disease stages, the disease-specific neuropathological features revealed by ubiquitinand P S129 -a-synuclein-specific antibodies were similar in mice with or without Parkin. However, the proportion of P S129 -asynuclein-immunoreactive neuronal cell bodies and neurites co-stained for ubiquitin was lower in the absence than in the presence of Parkin, suggesting less advanced synucleinopathy. Moreover, sensorimotor impairment and manifestation of the neurodegenerative phenotype due to overproduction of human a-synuclein were significantly delayed in Parkindeficient mice. These findings raise the possibility that effective compensatory mechanisms modulate the phenotypic expression of disease in parkin-related parkinsonism. Citation: Fournier M, Vitte J, Garrigue J, Langui D, Dullin J-P, et al. (2009) Parkin Deficiency Delays Motor Decline and Disease Manifestation in a Mouse Model of Synucleinopathy. PLoS ONE 4(8): e6629.

Physiology & Behavior, 1985

Physiology & Behavior, 1989

Exploratory, locomotor and ambulatory activities were measured in nine independent groups of thre... more Exploratory, locomotor and ambulatory activities were measured in nine independent groups of three inbred strains of mice (BALB/cBy, C57BL/6J and DBA/2J), at three different ages (150 days, 400 days and 750 days). The results show that for two of the three variables, the age-related changes present different patterns as a function of strain. The genetic and/or environmental correlates of the reactivity to aging may thus depend on the behavioral trait under study.

Physiology & Behavior, 1983

CARLIER, M., P. ROUBERTOUX AND CH. COHEN-SALMON. Early development in mice: 1. Genotype and postn... more CARLIER, M., P. ROUBERTOUX AND CH. COHEN-SALMON. Early development in mice: 1. Genotype and postnatal maternal effects. PHYSIOL BEHAV 30(6) 837-844, 1983.--The co-actions of genetic effects and the post-natal maternal rearing environment on the development of weight, 9 reflex responses, and survival have been tested by the cross-fostering method in two inbred mice strains---CBA/H and NZB. Pups of the two strains were not treated differentially by the mothers and experimental handling did not systematically affect pup development. Comparisons of unfostered, infostered, and cross-fostered pups show (1) in 16 cases out of 34, reflex development was affected by the pup strain, and in 10 cases out of 34 by the foster mother strain; (2) survival is only affected by the pup strain; (3) weight development is affected by strain of both the pup and the mother as well as their interactions. The adopted pups' scores were situated outside the range of the two non-adopted groups for certain reflexes as well as for weight. Two non-exclusive hypotheses are proposed: the mother strain can affect pup development (1) either through differences in stimulation provided by the mothers (2) or through differences in milk composition.