Neurocentre Magendie

Michel LE-MOAL


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414 publication(s) depuis Janvier 1966:

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01/2011 | Ann N Y Acad Sci   IF 4.7
Individual vulnerability to addiction.
Swendsen J, Le Moal M

The process of addiction is often studied in the neurosciences as a function of the quantity or type of substance consumed, with the ultimate goal of counteracting these effects by other pharmacological means. However, epidemiology and clinical research have extensively demonstrated that most individuals who use drugs do not develop dependence. Numerous factors may explain an individual's propensity to addiction. This review discusses these paradigms and summarizes research on individual differences that encompass cultural and sociodemographic factors, psychiatric or psychological vulnerability, and biological or genetic propensity to addiction. Although these different factors often interact in the expression of vulnerable phenotypes, it is possible to alter or control specific sources of vulnerability. For these reasons, integrating individual vulnerability to addiction across different research disciplines is likely to provide the greatest advances for intervention and prevention efforts.

12/2010 | Int J Vitam Nutr Res   IF 0.8
Paradoxical effect of severe dietary restriction on Long-Evans rat life span.
Abalan F, Mayo W, Simon H, Le Moal M

It has been firmly established that the longevity of 20- to 60%-calorie-restricted rodents, with malnutrition (essential nutrients deficiency) being avoided, is increased when compared to ad libitum fed rodents. However, the effects on life span of severe dietary restriction (i. e. malnutrition), with limited weight loss, remained unknown. The purpose of this 4-year study was to investigate the effects on longevity of a severe form of dietary restriction, with limited and controlled weight loss. To this end, a group of male Long-Evans rats severely dietary restricted (SDR group), with a weight loss throughout the experiment

07/2009 | J Clin Microbiol   IF 3.7
Partial atlE sequencing of Staphylococcus epidermidis strains from prosthetic joint infections.
Sivadon V, Rottman M, Quincampoix JC, Prunier E, Le Moal M, de Mazancourt P, Hoffmeyer P, Lortat-Jacob A, Piriou P, Judet T, Bernard L, Gaillard JL

Partial atlE sequencing (atlE nucleotides 2782 to 3114 [atlE(2782-3114)]) was performed in 41 Staphylococcus epidermidis isolates from prosthetic joint infections (PJIs) and 44 isolates from skin as controls. The atlE(2782-3114) allele 1 (type strain sequence) was significantly more frequent in PJI strains (38/41 versus 29/44 in controls; P = 0.0023). Most PJI strains were positive for mecA, icaA/icaD, and IS256, and most belonged to the sequence type 27 subgroup, suggesting the involvement of few related clones.

05/2009 | Pharmacopsychiatry   IF 1.8
Drug abuse: vulnerability and transition to addiction.
Le Moal M

Intrinsic vulnerability is central to the transition of recreational drug use to misuse. Several factors contribute to vulnerability, inherent or acquired, and they account for the huge individual differences observed concerning the propensity to enter in the addiction process. Some of the multifactional causes for a vulnerable phenotype will be examined: genetic factors, age and gender influences, various comorbidities and epidemiological observations. Stress-induced vulnerability will be particularly reviewed because it provides a good model for a pathophysiological research and for relating environmental events to biological consequences of drug vulnerability, namely through the striato-cortical dopamine system. Experimental studies are generally blind concerning these historical factors that contribute vulnerability and a critical evaluation of current animal models is needed. The transition of the last stage of the process, addiction, is conceptualized as a progression from homeostasis to allostasis and then, to pathology.

02/2009 | Eur J Neurosci   IF 2.9
Age-dependent effect of prenatal stress on hippocampal cell proliferation in female rats.
Koehl M, Lemaire V, Le Moal M, Abrous DN

Stressors occurring during pregnancy can alter the developmental trajectory of offspring and lead to, among other deleterious effects, cognitive deficits and hyperactivity of the hypothalamo-pituitary-adrenal axis. A recent feature of the prenatal stress (PS) model is its reported influence on structural plasticity in hippocampal formation, which sustains both cognitive functions and stress responsiveness. Indeed, we and others have previously reported that males exposed to stress in utero are characterized by a decrease in hippocampal cell proliferation, and consequently neurogenesis, from adolescence to senescence. Recent studies in females submitted to PS have reported conflicting results, ranging from no effect to a decrease in cell proliferation. We hypothesized that changes in cell proliferation in PS female rats are age dependent. To address this issue, we examined the impact of PS on hippocampal cell proliferation in juvenile, young, middle-aged and old females. As hypothesized, we found an age-dependent effect of PS in female rats as cell proliferation was significantly decreased only when animals reached senescence, a time when adrenal gland weight also increased. These data suggest that the deleterious effects of PS on hippocampal cell proliferation in females are either specific to senescence or masked during adulthood by protective factors.

12/10/2008 | Philos Trans R Soc Lond B Biol Sci   IF 5.8
Review. Neurobiological mechanisms for opponent motivational processes in addiction
Koob G F, Le Moal M

The conceptualization of drug addiction as a compulsive disorder with excessive drug intake and loss of control over intake requires motivational mechanisms. Opponent process as a motivational theory for the negative reinforcement of drug dependence has long required a neurobiological explanation. Key neurochemical elements involved in reward and stress within basal forebrain structures involving the ventral striatum and extended amygdala are hypothesized to be dysregulated in addiction to convey the opponent motivational processes that drive dependence. Specific neurochemical elements in these structures include not only decreases in reward neurotransmission such as dopamine and opioid peptides in the ventral striatum, but also recruitment of brain stress systems such as corticotropin-releasing factor (CRF), noradrenaline and dynorphin in the extended amygdala. Acute withdrawal from all major drugs of abuse produces increases in reward thresholds, anxiety-like responses and extracellular levels of CRF in the central nucleus of the amygdala. CRF receptor antagonists block excessive drug intake produced by dependence. A brain stress response system is hypothesized to be activated by acute excessive drug intake, to be sensitized during repeated withdrawal, to persist into protracted abstinence and to contribute to stress-induced relapse. The combination of loss of reward function and recruitment of brain stress systems provides a powerful neurochemical basis for the long hypothesized opponent motivational processes responsible for the negative reinforcement driving addiction.

04/2008 | Bull Acad Natl Med   IF 0.3
[Neurosciences in Bordeaux]
Le Moal M, Battin J, Bioulac B, Bourgeois M L, Henry P, Vital C, Vincent J D


2008 | Annu Rev Psychol   IF 20
Addiction and the brain antireward system
Koob G F, Le Moal M

A neurobiological model of the brain emotional systems has been proposed to explain the persistent changes in motivation that are associated with vulnerability to relapse in addiction, and this model may generalize to other psychopathology associated with dysregulated motivational systems. In this framework, addiction is conceptualized as a cycle of decreased function of brain reward systems and recruitment of antireward systems that progressively worsen, resulting in the compulsive use of drugs. Counteradaptive processes, such as opponent process, that are part of the normal homeostatic limitation of reward function fail to return within the normal homeostatic range and are hypothesized to repeatedly drive the allostatic state. Excessive drug taking thus results in not only the short-term amelioration of the reward deficit but also suppression of the antireward system. However, in the long term, there is worsening of the underlying neurochemical dysregulations that ultimately form an allostatic state (decreased dopamine and opioid peptide function, increased corticotropin-releasing factor activity). This allostatic state is hypothesized to be reflected in a chronic deviation of reward set point that is fueled not only by dysregulation of reward circuits per se but also by recruitment of brain and hormonal stress responses. Vulnerability to addiction may involve genetic comorbidity and developmental factors at the molecular, cellular, or neurocircuitry levels that sensitize the brain antireward systems.


08/2007 | Psychoneuroendocrinology   IF 4.8
Historical approach and evolution of the stress concept: a personal account.
Le Moal M

As a matter of research or as a process, stress remains one of the most cited construct in biomedical literature; a medline survey accounts for more than 210,000 citations since 1970. It is difficult to define. It is frequently used in a vague manner, including undifferently the agent, the process, and the response. The concept is multidimensional and composite, including emotion and arousal. Stress has an implicit: it implies alteration of a theoretical balance or equilibrium within physiological systems, and it seems to characterize a process leading to disease. Large individual differences exist in the way to react to a stressor. Psychological and cognitive determinants are central for the course of the process. The homeostasis concept is not useful anymore and has been replaced by the more accurate and flexible concept of allostasis. The physiological hormonal and neural bases of this process are now identified. New perspectives identify stressors, chronic or not, to be a source of vulnerabilities through epigenetic mechanisms and a series of biobehavioral disorders characteristic of our modern civilizations. The evolution of the concept is not linear. It has been enriched by recent neurobiological-neuroendocrinological discoveries and also by behavioral-cognitive sciences.