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  • 1
    Keywords: brain ; EXPRESSION ; MODEL ; MODELS ; SYSTEM ; COHORT ; GENE ; PROTEIN ; transcription ; DRUG ; MICE ; RESPONSES ; MECHANISM ; TRANSCRIPTION FACTOR ; RATS ; mechanisms ; BINDING ; ALPHA ; CREB ; ELEMENT ; ELEMENT-BINDING PROTEIN ; ISOFORM ; MUTANT ; NERVOUS-SYSTEM ; NO ; TARGETED MUTATION ; DECREASE ; STRESS ; MUTATION ; MODULATION ; REGION ; REGIONS ; Jun ; INVOLVEMENT ; BEHAVIOR ; FOOD ; LACKING ; BINDING PROTEIN ; molecular ; BINDING-PROTEIN ; MOLECULAR-MECHANISM ; DEPENDENCE ; NEURONS ; KNOCKOUT MICE ; ADDICTION ; CERULEUS ; conditioned place preference ; emotional behavior ; locus coeruleus ; LOCUS-COERULEUS NEURONS ; MOLECULAR-MECHANISMS ; NEURAL PLASTICITY ; opiate addiction ; OPIATE-WITHDRAWAL
    Abstract: The transcription factor cAMP-responsive element binding protein (CREB) has been shown to regulate different physiological responses including drug addiction and emotional behavior. Molecular changes including adaptive modifications of the transcription factor CREB are produced during drug dependence in many regions of the brain, including the locus coeruleus (LC), but the molecular mechanisms involving CREB within these regions have remained controversial. To further investigate the involvement of CREB in emotional behavior, drug reward and opioid physical dependence, we used two independently generated CREB-deficient mice. We employed the Cre/loxP system to generate mice with a conditional CREB mutation restricted to the nervous system, where all CREB isoforms are lacking in the brain (Creb / (NesCre)). A genetically defined cohort of the previously described hypomorphic Creb / (alphaDelta) mice, in which the two major transcriptionally active isoforms (alpha and Delta) are disrupted throughout the organism, were also used. First, we investigated the responses to stress of the CREB-deficient mice in several paradigms, and we found an increased anxiogenic-like response in the both Creb / mutant mice in different behavioral models. We investigated the rewarding properties of drugs of abuse (cocaine and morphine) and natural reward (food) using the conditioned place-preference paradigm. No modification of motivational responses of morphine, cocaine, or food was observed in mutant mice. Finally, we evaluated opioid dependence by measuring the behavioral expression of morphine withdrawal and electrophysiological recordings of LC neurons. We showed an important attenuation of the behavioral expression of abstinence and a decrease in the hyperactivity of LC neurons in both Creb / mutant mice. Our results emphasize the selective role played by neuronal CREB in emotional-like behavior and the somatic expression morphine withdrawal, without participating in the rewarding properties induced by morphine and cocaine
    Type of Publication: Journal article published
    PubMed ID: 15029152
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  • 2
    ISSN: 1432-1238
    Keywords: Bacteriological surveillance ; Septicaemias, incidence, by Serratia sp., by Klebsiella sp., epidemic outbreaks ; Intensive Care Unit
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The high rate of septicaemias (20%, 19% and 14%) observed in our Intensive Care Unit (ICU) during the first 3 years was due to an epidemic incidence of Serratia sp. (S) (26% during the first year) and Klebsiella sp. (K) (25% during the third) and decreased significantly in the following 6 years (mean incidence of 11%) (p〈0.01). During this epidemic phase these organisms were isolated quite frequently (between a 14% and a 6%) from all patients admitted. The K was more regularly present, for the mean time intervals free of its bacteriological presence were shorter (11 days) than those of S (27 days) (p〈0.01). The K was isolated in more patients (160) than S (79) (p〈0.01) and in more samples (360) than S (235) (p〈0.01), but caused less secondary septicaemias per colonized patient (7% versus 29%) (p〈0.01). In 59% of all S septicaemias the organism was previously isolated in other culture, while this was observed in only 34% of K septicaemias (x2=3.78, p=0.052). The large variations in the incidence of septicaemias within our ICU, the appearance of sequential epidemic outbreaks, with a different behaviour of S and K and the individual risk of septicaemia of patients colonized by these organisms are noted.
    Type of Medium: Electronic Resource
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