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  • 1
    Keywords: CELLS ; Germany ; VENTILATION ; GENE ; GENES ; PROTEIN ; METABOLISM ; MICE ; FAMILY ; BINDING ; DOWN-REGULATION ; NK cells ; PHENOTYPE ; RAT-BRAIN ; THYROID-HORMONE ; LEVEL ; function ; ANTAGONISTS ; BROWN ADIPOSE-TISSUE ; CEREBRAL-CORTEX ; MODIFIED HOLE BOARD ; PRECHORDAL PLATE ; REDUCED EXPRESSION ; TYPE-2 IODOTHYRONINE DEIODINASE ; ZEBRAFISH DKK1
    Abstract: dickkopf (dkk) genes encode a small family of secreted Wnt antagonists, except for dkk3, which is divergent and whose function is poorly understood. Here, we describe the generation and characterization of dkk3 mutant mice. dkk3-deficient mice are viable and fertile. Phenotypic analysis shows no major alterations in organ morphology, physiology, and most clinical chemistry parameters. Since Dkk3 was proposed to function as thyroid hormone binding protein, we have analyzed deiodinase activities, as well as thyroid hormone levels. Mutant mice are euthyroid, and the data do not support a relationship of dkk3 with thyroid hormone metabolism. Altered phenotypes in dkk3 mutant mice were observed in the frequency of NK cells, immunoglobulin M, hemoglobin, and hematocrit levels, as well as lung ventilation. Furthermore, dkk3-deficient mice display hyperactivity
    Type of Publication: Journal article published
    PubMed ID: 16508007
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Alcohol deprivation effect ; Ethanol ; Opiate antagonist ; Relapse ; Treatment regimen ; Voluntary alcohol self-administration
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Opiate antagonists are promising pharmacotherapeutic agents for the treatment of alcohol dependence, reducing craving and relapse rates in weaned alcoholics. However, preclinical findings indicate that they can also increase ethanol consumption and preference in animals with a strong liking for ethanol, depending on the dose and treatment regimen. Objective: The present study examined the effects of chronic, intermittent and acute opiate antagonist treatment on the alcohol deprivation effect (ADE) in long-term ethanol- experienced rats, which is an animal model of craving and relapse. Methods: Long-term ethanol-experienced rats were either implanted with mini-osmotic pumps delivering 0, 0.5 or 1 mg/kg per hour naloxone (chronic treatment) or received intermittent naltrexone injections (2×5 mg/kg per day SC). Effects of chronic and intermittent treatment on the ADE were studied in a four-bottle home cage drinking paradigm. In a second experiment, long-term ethanol-experienced rats trained in an operant ethanol self-administration paradigm received acute naltrexone treatment (0, 0.1, 1 or 10 mg/kg SC) before a 23-h session either during basal drinking or during the ADE. Results: Chronic naloxone treatment increased ethanol preference during the ADE. Intermittent naltrexone treatment at a dose comparable to the lower dose of chronic treatment moderately attenuated the ADE. Acute naltrexone treatment selectively reduced lever pressing for ethanol both during the ADE and during basal drinking only at the lowest dose, whereas higher doses also suppressed water intake. The ethanol-specific suppressant effect on the ADE was long lasting. Concerning basal drinking, however, naltrexone had a long lasting reductive effect only on lever pressing for water. Conclusions: A low dose of naltrexone and an intermittent treatment regimen seem to be necessary to maintain a specific reduction in ethanol intake in individuals with a high motivation to consume ethanol. These findings are consistent with the notion that, at low doses, opiate antagonists reduce the reward value of reinforcers.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-1463
    Keywords: Keywords: Alcoholism, craving, relapse, acamprosate, naltrexone.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. A new animal model of alcoholism has been developed. Rats derived from this model show certain characteristics: (i) they have an incentive demand to consume alcohol, (ii) they exhibit relapse-like drinking even after a very long time of abstinence, (iii) they show tolerance to alcohol and have mild signs of physical withdrawal during the onset of abstinence, and (iv) during abstinence they also exhibit a psychological withdrawal syndrome consisting of enhanced anxiety-related behaviour and hyperreactivity to stressful situations. Anti-craving drugs such as acamprosate and naltrexone which proved to be effective in human alcoholics to prevent relapse were also effective in our animal model. Thus, both compounds suppressed the alcohol deprivation effect which is used as a measure for craving and relapse. It is concluded that this pharmacological validation of our model demonstrates the predictive value of our model and enables us to further characterize putative anti-craving drugs and neurobiological mechanisms of addictive behaviour.
    Type of Medium: Electronic Resource
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