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  • 2000-2004  (7)
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Year
  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Journal of neurochemistry 86 (2003), S. 0 
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Previous studies showed that prolonged access to cocaine or heroin self-administration (long access, or LgA) produces an escalation in drug intake not observed with limited access to the drug (short access, or ShA). The present experiment employed in vivo microdialysis to test the role of alterations in drug pharmacokinetics and/or efficacy in increasing dopamine (DA) levels in the nucleus accumbens (NAcc) during cocaine intake escalation. In experiment 1, both ShA and LgA rats were challenged with passive intravenous administration of cocaine (0.125–1 mg/injection). Regardless of the doses tested, there was no difference between groups in the ability of cocaine to increase NAcc DA levels and no group differences in the temporal profile of dialysate cocaine levels. In experiment 2, cocaine and DA concentrations were measured during cocaine self-administration. Self-administration produced sustained increases of DA in the NAcc with LgA rats maintaining greater steady levels of DA (750% of baseline) than ShA rats (400% of baseline). The difference in the LgA versus ShA rats was not due to differences in the efficacy of cocaine to elevate DA levels, or in the rate of cocaine metabolism, but was directly related to the amount of self-administered cocaine. These findings show that changes in cocaine efficacy or pharmacokinetics do not play a critical role in cocaine intake escalation.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Carfax Publishing, part of the Taylor & Francis Group
    Addiction 95 (2000), S. 0 
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: Craving has various meanings but can be defined generally in terms of a desire for the previously experienced effects of ethanol. Animal models provide a means by which to study the underlying mechanisms associated with craving and are most useful when they fulfill the requirements for predictive validity and reliability. Craving is a key part of the process of addiction that can lead to relapse and is conceptualized as having at least three components: preoccupation/anticipation, binge/intoxication and withdrawal/negative affect. Animal models of craving are hypothesized at this time to involve three domains of motivation to take drugs: excessive drinking, negative affective states and conditioned reinforcement. Excessive drinking includes the alcohol deprivation effect, drinking during withdrawal and drinking after a history of dependence. Models of the negative affective state include increases in brain reward thresholds, and conditioned reinforcement models include cue-induced resistance to extinction or cue-induced reinstatement. Experimental psychology is a rich resource of sensitive behavioral techniques by which to measure hypothetical constructs associated with the motivation to drink ethanol. Rigorous tests of predictive validity and reliability will be necessary to make them useful for understanding the neurobiology of craving and for the development of new medications for treating craving.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    European journal of neuroscience 16 (2002), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Whereas the role of dopaminergic tone in the cortico-striatal-thalamic system is well-established, the role of endogenous opioids in the function of this system is less understood. We show that Borna disease virus infection of adult rats results in an increase in preproenkephalin transcripts in the striatum of Borna-infected rats, a region important for forming coordinated sequential motor actions and in developing programmes of thought and motivation. Stereotypic behaviours and dyskinesias, the clinical hallmarks of infection in adult Lewis rats (BD rats), are accompanied by a disrupted pattern of immediate early gene c-fos activation in the motor thalamus, with significance for the breakdown in coordinated sequential motor actions. We also find increased preproenkephalin in infected cultured neuroblastoma and rat foetal glial cells. The expression pattern of enkephalin mRNA in vivo and in vitro suggest that increased enkephalin function is one of the neuropharmacological means by which Borna disease virus causes motor disease of animals and possibly cognitive and affective disease in man, and further suggest that enkephalins play a critical role in the maintenance of a balanced tone of activity in the cortico-basal ganglia-thalamo-cortical loops.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science, Ltd
    European journal of neuroscience 17 (2003), S. 0 
    ISSN: 1460-9568
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study investigated the effects of self-administered cocaine on brain reward function, measured by intracranial self-stimulation (ICSS) reward thresholds in rats. Self-administration of 10 and 20 cocaine injections (0.25 mg per injection, equivalent to 4.94 ± 0.23 and 9.88 ± 0.46 mg/kg, self-administered over 40 ± 6.9 and 99 ± 11.9 min, respectively) lowered reward thresholds 15 min later, indicating a facilitation of rewarding ICSS, but had no effect at 2, 24 or 48 h after administration. Thus, self-administration of low cocaine doses did not cause persistent changes in brain reward function. Forty cocaine injections (19.64 ± 0.94 mg/kg; self-administered over 185 ± 10.9 min) also transiently lowered reward thresholds 15 min later, while significant threshold current elevations were observed at 2 and 24 h after administration, indicating persistent withdrawal-like reward deficits. Finally, 80 cocaine injections (39.53 ± 1.84 mg/kg, self-administered over 376 ± 19.9 min) significantly elevated thresholds 2 and 48 h after self-administration, but not at 24 h. Threshold currents also tended to be elevated 15 min after self-administration. Overall, these data suggest that as the amount of self-administered cocaine increases the motivation to consume further cocaine may be shifted, from obtaining the rewarding actions of cocaine to avoidance and alleviation of a cocaine-induced negative affective state.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Corticotropin-releasing hormone (Crh) is a critical coordinator of the hypothalamic-pituitary-adrenal (HPA) axis. In response to stress, Crh released from the paraventricular nucleus (PVN) of the hypothalamus activates Crh receptors on anterior pituitary corticotropes, resulting in release of ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature medicine 10 (2004), S. 340-341 
    ISSN: 1546-170X
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Addiction is characterized by three major elements: compulsion to seek and take the drug, loss of control in limiting intake, and the emergence of negative emotional states, such as anxiety and irritability, when access to the drug is cut off. While drugs of abuse are extremely diverse in their ...
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Urocortin is a member of the corticotropin-releasing hormone peptide family and is found in many discrete brain regions. The distinct expression pattern of urocortin suggests that it influences such behaviors as feeding, anxiety and auditory processing. To better define the physiological roles of ...
    Type of Medium: Electronic Resource
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