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  • 1
    Keywords: brain ; PEPTIDE ; RECEPTOR ; CELLS ; EXPRESSION ; GROWTH ; INHIBITOR ; BLOOD ; CELL ; GENE ; GENES ; PROTEIN ; transcription ; METABOLISM ; MICE ; RELEASE ; ACTIVATION ; TRANSCRIPTION FACTOR ; IMPACT ; hepatocytes ; BINDING ; PHOSPHORYLATION ; SIGNAL ; ACID ; CREB ; ELEMENT-BINDING PROTEIN ; TRANSGENIC MICE ; hormone ; DISRUPTION ; BODY ; MUTANT MICE ; HYPOPLASIA ; BINDING PROTEIN ; LOSSES ; SIGNALS ; EXPANSION ; CAMP RESPONSE ELEMENT ; CREB FUNCTION ; HORMONE-RELEASING-HORMONE ; NEURAL STEM
    Abstract: The principal regulation of body growth is via a cascade of hormone signals emanating from the hypothalamus, by release of GHRH, which then directs the somatotroph cells of the pituitary to release GH into the blood stream. This in turn leads to activation of signal transducer and activator of transcription 5-dependent expression of genes such as IGF-1 in hepatocytes, acid labile substance, and serine protease inhibitor 2.1, resulting in body growth. Here, using conditional cAMP response element binding protein ( CREB) mutant mice, we show that loss of the CREB transcription factor in the brain, but not the pituitary, results in reduced postnatal growth consistent with dwarfism caused by GH deficiency. We demonstrate that although there appears to be no significant impact upon the expression of GHRH mRNA in CREB mutant mice, the amount of GHRH peptide is reduced. These findings show that CREB is required for the efficient production of GHRH in hypothalamus, in addition to its previously reported role in pituitary GH production and somatotroph expansion
    Type of Publication: Journal article published
    PubMed ID: 16141355
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  • 2
    ISSN: 1432-2072
    Keywords: Morphine self-administration ; Extinction probe ; Dose response ; Multiple reinforcers ; Food intake ; Water intake ; 24-Hour sessions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Responding by six rats was maintained under a concurrent chained fixed-ratio 1, fixed-ratio 9 schedule (conc chain FR1 FR9) of food, water, and morphine presentations. The subjects had continuous access to the schedule contingencies on a reversed 12-h light-dark cycle. Local rates and temporal patterns were very similar for responding maintained by the three reinforcers with food and water intake occurring predominantly during the dark cycle, while morphine infusions were evenly distributed. Food and water extinction (24-h duration) decreased the number of ratios completed on both the food and water levers. Moreover, food extinction resulted in a large increase in I.V. morphine self-administration. Morphine extinction increased responding on the morphine lever while almost eliminating responding on the water lever. Changes in the dose of morphine (2.5–40 mg/kg/injection) did not significantly affect food and water intake, but were inversely related to responding on the morphine lever. Saline substitutions resulted in effects similar to those observed during morphine extinction. The schedule used in this study provides a method for examining the specificity of a number of pharmacological and neurochemical manipulations.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Cocaine ; Heroin ; Ibogaine Self-administration ; Scheduled-controlled behavior Fixed ratio
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of ibogaine (40 and 80 mg/kg, IP), an indole alkaloid proposed for the treatment of drug abuse, were determined in three different groups of rats responding under an FR10 schedule of food, cocaine or heroin reinforcement. Ibogaine (80 mg/kg, IP) given 60 min before the start of the session resulted in a 97% decrease in the number of ratios completed under the food reinforcement schedule and resulted in a decrease in responding the following day. Neither 40 mg/kg ibogaine given 60 min prior to the session nor 80 mg/kg given 24 h before the session suppressed responding maintained by cocaine infusions (0.33 mg/infusion). Pretreatment with 80 mg/kg ibogaine either 60 or 90 min prior to the session suppressed cocaine self-administration on the day it was administered and the longer pretreatment continued to suppress responding for 48 h. Responding maintained by heroin (18 µg/infusion) was the most sensitive to the effects of ibogaine. Both 40 and 80 mg/kg ibogaine resulted in an almost complete suppression of responding following a 60-min pretreatment period. Responding maintained by heroin returned to control levels the day following the administration of ibogaine.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Drug self-administration ; Cocaine Tolerance ; Response-dependent Response-independent ; Drug abuse ; Lever press ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The drug self-administration paradigm is routinely used to assess the abuse liability of psychoactive compounds. Investigations of the behavioral effects of drug use, however, often involve the response-independent (experimenter-delivered) administration of the compound. It is frequently assumed that response-independent presentation of a compound has the same effects as response dependent deliveries. The present study examined directly the effects of response-dependent (self-administered) versus response-independent (experimenter- delivered) administration of cocaine on food intake and lethality. Littermate triads were exposed to either cocaine (0.33 mg/infusion) or saline using a yoked-box procedure. One member of the triad self-administered the drug under a fixed-ratio 2 schedule. The other two rats received response-independent infusions of either cocaine or saline. Groups of triads were exposed to two different cocaine access conditions. Daily sessions were terminated after 6 h for one group and after the delivery of 80 infusions for the other. The mean number of infusions delivered each session was 47 (±12) and 70 (±11), respectively, for the 6-h and 80-infusion condition. Under the 80-infusion condition, response-independent infusions of cocaine resulted in a significantly higher rate of mortality compared to littermates self-administering identical amounts of the drug. A fewer number of deaths occurred under 6-h condition; however, only rats exposed to response-independent infusions died under both access conditions. These data indicate that the presence or absence of response dependency can profoundly alter the lethal effects of cocaine.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Quality of life research 3 (1994), S. S77 
    ISSN: 1573-2649
    Keywords: Behavioural intervention ; chronic pain management ; depression ; health care expenditure ; somatization
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The two defining features of somatization are numerous self-reported physical symptoms and excessive health care seeking. This may be due to a lowered perceptual threshold for perceiving and reporting bodily symptoms, amplification or misinterpretation of those symptoms, or underlying psychiatric disturbance. Recurrent pain is the most common somatic symptom reported. True somatization disorder is very rare (〈1%) and requires a DSM-III-R diagnosis of at least 13 different physical symptoms which cannot be explained by, or are in gross excess of physical findings, and have caused the patients to seek health care or alter their lifestyles. However, researchers have argued that a spectrum of severity for somatization exists, and this is supported by epidemiological research. Available data also indicate that behavioural interventions may show long-term cost-effectiveness in the management of chronic pain. Chronic pain dysfunction appears to place a disproportionate burden on overall health care expenditure for chronic pain patients.
    Type of Medium: Electronic Resource
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