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Michel LE-MOAL

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414 publication(s) since Janvier 1966:

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02/2006 | Psychopharmacology (Berl)   IF 3.2
Preexposure during or following adolescence differently affects nicotine-rewarding properties in adult rats
Adriani W, Deroche-Gamonet V, Le Moal M, Laviola G, Piazza P V

RATIONALE: Many people come in contact with psychoactive drugs, yet not all of them become addicts. Epidemiology shows that a late approach with cigarette smoking is associated with a lower probability to develop nicotine dependence. Exposure to nicotine during periadolescence, but not similar exposure in the postadolescent period, increases nicotine self-administration in rats, but underlying mechanisms remain poorly understood. OBJECTIVE: We investigated whether exposure to nicotine during or after adolescence would alter rewarding properties of the same drug at adulthood, as assessed by place conditioning. MATERIALS AND METHODS: Periadolescent (PND 34-43) or postadolescent (PND 60-69) rats were injected with saline or nicotine (0.4 mg kg(-1)) for 10 days. The rats received three pairings with saline and three pairings with nicotine (0, 0.3, or 0.6 mg kg(-1)) 5 weeks after pretreatment. The rats were then tested for place conditioning in a drug-free state. RESULTS: Upon first exposure to the apparatus, animals pretreated with nicotine during adolescence showed elevated novelty-induced activation. The 0.3 (but not the 0.6) mg kg(-1) dose failed to produce both ongoing locomotor sensitization and place conditioning in animals pretreated with nicotine following adolescence. This suggests a rightward shift in the dose-response curve, namely, a reduced efficacy of nicotine. Conversely, the same dose was effective in saline-pretreated controls and noteworthy in rats pretreated during adolescence. CONCLUSION: Exposure following the adolescent period might diminish the risk to develop nicotine dependence. As for human implications, findings are consistent with a reduced vulnerability to nicotine addiction in people who start smoking late in their life.

11/2005 | Nat Neurosci   IF 19.9
Plasticity of reward neurocircuitry and the 'dark side' of drug addiction
Koob G F, Le Moal M

Drug seeking is associated with activation of reward neural circuitry. Here we argue that drug addiction also involves a 'dark side'--a decrease in the function of normal reward-related neurocircuitry and persistent recruitment of anti-reward systems. Understanding the neuroplasticity of the dark side of this circuitry is the key to understanding vulnerability to addiction.

12/10/2005 | Brain Res   IF 3.1
Chronic exposure to an environmental noise permanently disturbs sleep in rats: inter-individual vulnerability
Rabat A, Bouyer J J, Aran J M, Le Moal M, Mayo W

Chronic exposure to an environmental noise (EN) induces sleep disturbances. However, discrepancies exist in the literature since many contradictory conclusions have been reported. These disagreements are largely due to inappropriate evaluation of sleep and also to uncontrolled and confounding factors such as sex, age and also inter-individual vulnerability. Based on a recently validated animal model, aims of the present study were (i) to determine the effects of a chronic exposure to EN on sleep and (ii) to evaluate the inter-individual vulnerability of sleep to EN. For this purpose, rats were exposed during 9 days to EN. Results show that a chronic exposure to EN restricts continually amounts of slow wave sleep (SWS) and paradoxical sleep (PS) and fragments these two sleep stages with no habituation effect. Results also evidence the existence of subpopulations of rats that are either resistant or vulnerable to these deleterious effects of EN on sleep and especially on SWS amounts, bouts number and bout duration. Furthermore, importance of SWS debt and daily decrease of SWS bout duration are correlated to each others and both correlate to the amplitude of the locomotor reactivity to novelty, a behavioral measure of reactivity to stress. This last result suggests that this psychobiological profile of subjects, known to induce profound differences in neural and endocrine systems, could be responsible for their SWS vulnerability under a chronic EN exposure.

08/2005 | J Clin Microbiol   IF 4.1
Molecular detection of Cellulosimicrobium cellulans as the etiological agent of a chronic tongue ulcer in a human immunodeficiency virus-positive patient.
Heym B, Gehanno P, Friocourt V, Bougnoux ME, Le Moal M, Husson C, Leibowitch J, Nicolas-Chanoine MH

Ulcerations appeared on the tongue of a 48-year-old human immunodeficiency virus-positive man. Histological findings of the biopsy specimen and the fact that the patient had resided in Louisiana led us to suspect 'American histoplasmosis'. A new ulcer appeared while the patient was being treated with itraconazole, and the gene for 16S rRNA of Cellulosimicrobium cellulans was amplified. The lesions healed during treatment with oral penicillin and azithromycin.

08/2005 | Eur J Neurosci   IF 2.8
Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus.
Dupret D, Montaron MF, Drapeau E, Aurousseau C, Le Moal M, Piazza PV, Abrous DN

During adulthood, new neurons are continuously added to the mammalian dentate gyrus (DG). An increasing number of studies have correlated changes in rates of dentate neurogenesis with memory abilities. One study based on subchronic treatment with the toxin methylazoxymethanol acetate (MAM) has provided causal evidence that neurogenesis is involved in hippocampal-dependent trace conditioning. In contrast, spatial learning is not impaired following MAM treatment. We hypothesized that this was due to the small residual number of new cells produced following MAM treatment. In the present experiment, we attempted to achieve a higher level of reduction of adult-generated cells following MAM treatment in young and aged rats. We found only a partial reduction of adult-generated cells in the DG. More importantly, independently of the age of the animals, MAM treatment at a dose necessary to reduce neurogenesis altered the overall health of the animals. In conclusion, the behavioural results obtained following subchronic treatment with high doses of MAM in adulthood must be interpreted with extreme caution.

04/2005 | Physiol Rev   IF 24
Adult neurogenesis: from precursors to network and physiology.
Abrous DN, Koehl M, Le Moal M

The discovery that the adult mammalian brain creates new neurons from pools of stemlike cells was a breakthrough in neuroscience. Interestingly, this particular new form of structural brain plasticity seems specific to discrete brain regions, and most investigations concern the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation (HF). Overall, two main lines of research have emerged over the last two decades: the first aims to understand the fundamental biological properties of neural stemlike cells (and their progeny) and the integration of the newly born neurons into preexisting networks, while the second focuses on understanding its relevance in brain functioning, which has been more extensively approached in the DG. Here, we propose an overview of the current knowledge on adult neurogenesis and its functional relevance for the adult brain. We first present an analysis of the methodological issues that have hampered progress in this field and describe the main neurogenic sites with their specificities. We will see that despite considerable progress, the levels of anatomic and functional integration of the newly born neurons within the host circuitry have yet to be elucidated. Then the intracellular mechanisms controlling neuronal fate are presented briefly, along with the extrinsic factors that regulate adult neurogenesis. We will see that a growing list of epigenetic factors that display a specificity of action depending on the neurogenic site under consideration has been identified. Finally, we review the progress accomplished in implicating neurogenesis in hippocampal functioning under physiological conditions and in the development of hippocampal-related pathologies such as epilepsy, mood disorders, and addiction. This constitutes a necessary step in promoting the development of therapeutic strategies.

01/2005 | Neurobiol Aging   IF 4.5
Pregnenolone sulfate enhances neurogenesis and PSA-NCAM in young and aged hippocampus.
Mayo W, Lemaire V, Malaterre J, Rodriguez JJ, Cayre M, Stewart MG, Kharouby M, Rougon G, Le Moal M, Piazza PV, Abrous DN

Age-dependent cognitive impairments have been correlated with functional and structural modifications in the hippocampal formation. In particular, the brain endogenous steroid pregnenolone-sulfate (Preg-S) is a cognitive enhancer whose hippocampal levels have been linked physiologically to cognitive performance in senescent animals. However, the mechanism of its actions remains unknown. Because neurogenesis is sensitive to hormonal influences, we examined the effect of Preg-S on neurogenesis, a novel form of plasticity, in young and old rats. We demonstrate that in vivo infusion of Preg-S stimulates neurogenesis and the expression of the polysialylated forms of NCAM, PSA-NCAM, in the dentate gyrus of 3- and 20-month-old rats. These influences on hippocampal plasticity are mediated by the modulation of the gamma-aminobutyric acid receptor complex A (GABA(A)) receptors present on hippocampal neuroblasts. In vitro, Preg-S stimulates the division of adult-derived spheres suggesting a direct influence on progenitors. These data provide evidence that neurosteroids represent one of the local secreted signals controlling hippocampal neurogenesis. Thus, therapies which stimulate neurosteroidogenesis could preserve hippocampal plasticity and prevent the appearance of age-related cognitive disturbances.

11/2004 | Exp Gerontol   IF 3.2
New insights into the role of neuroactive steroids in cognitive aging.
Vallee M, George O, Vitiello S, Le Moal M, Mayo W

The aim of this article is to describe neuroactive steroid research that has been focused on their physiological role in cognitive aging, an attractive new field in experimental gerontology. Neuroactive steroids have been recently proposed as biomarkers of cognitive aging, however, their specific functions have not yet been fully established. For instance, data emerging from human and animal studies suggest a complex relationship between neuroactive steroids and/or metabolites and cognitive processes during aging. Thus, a better knowledge of neuroactive steroid brain distribution and function could broaden our understanding of their physiological roles and lead to novel and more effective treatments for the management of age-related brain disorders. To this end, newly developed sensitive, specific, and accurate mass spectrometry assays may allow the quantification of neuroactive steroids in discrete brain regions and greatly contribute to unravel their role in age-related cognitive deficits.

01/06/2004 | J Neurosci Res   IF 2.7
Sleep-wake states and cortical synchronization control by pregnenolone sulfate into the pedunculopontine nucleus.
Darbra S, George O, Bouyer JJ, Piazza PV, Le Moal M, Mayo W

Cholinergic neurons of the pedunculopontine tegmentum nucleus (PPT) are crucial for initiation and maintenance of electroencephalographic (EEG) desynchronization states like paradoxical sleep and wakefulness. These neurons are regulated by classical neurotransmitter systems from the pontomesencephalic reticular formation and basal ganglia. In addition to this regulation, PPT neuron activity could be modulated by endogenous neurosteroids and particularly by pregnenolone sulfate (PREG-S) because synthesis enzymes of this neurosteroid are present in this area and peripheral administrations of PREG-S affect sleep-wakefulness states. To test this hypothesis, we studied the effects of different doses of PREG-S infusion into the PPT on sleep-wakefulness states in rats. Our results show dose-dependent effects of PREG-S on sleep-wakefulness states. Low concentration of PREG-S (5 ng) increased the amount of paradoxical sleep without any modification of slow wave sleep and wakefulness. High level of PREG-S (10 and 20 ng) increased paradoxical sleep and slow wave sleep together with an increase of delta power and a decrease of theta power during wakefulness. Dependent on the doses used, PREG-S thus can promote paradoxical sleep alone or the global propensity to fall asleep, impairing the quality of wakefulness. These results unveil a new regulation pathway for PPT neurons and strengthen the role of PREG-S in sleep-wakefulness regulation.

06/2004 | Behav Neurosci   IF 2.5
Early and later adoptions differently modify mother-pup interactions.
Darnaudery M, Koehl M, Barbazanges A, Cabib S, Le Moal M, Maccari S

Life events occurring during the perinatal period have strong long-term effects. In rats, prenatal stress, postnatal maternal separations, or adoptions at different periods are known to affect behavior and reactivity to stress in offspring. To determine the role of maternal factors on differential outcome adoptions, the authors investigated interactions between pups and the adopting mothers by assessing both pups' ultrasound emissions and maternal behavior. Early and late adoptions increased mother care at the moment of adoption and during mother-infant reunion after a separation procedure. However, although early adoption induced a decrease in pups' ultrasound emissions in response to a stressful separation, later adoptions enhanced it. Results suggest a sensitive period during which fostering may change pups' and dams' behavior.