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  • 1
    Electronic Resource
    Electronic Resource
    Dark side of drug dependence (1994)
    [s.l.] : Nature Publishing Group
    Nature 371 (1994), S. 108-109 
    Details
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] ADDICTIVE drugs - such as psychomotor stimulants (cocaine and amphetamines), depressants of the central nervous system (ethanol) and opiate narcotics (heroin and morphine) - in part produce their re-warding effects of euphoria or pleasure through an interaction with the mesolim-bic dopamine system. ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/371108a0
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  • 2
    Electronic Resource
    Electronic Resource
    Peripheral modulation of learning and memory: enkephalins as a model system (1992)
    Springer
    Psychopharmacology 109 (1992), S. 347-364 
    Details
    ISSN: 1432-2072
    Keywords: Modulation ; Learning ; Memory ; Enkephalins ; Autonomic systems ; Circumventricular organs ; Blood-brain barrier
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Extensive research on the effects of enkephalins on conditioning is reviewed and used as the basis for a model of peripheral modulation of learning and memory. An overall theme emphasized throughout our discussion is that these peptides can influence the strength with which a memory is acquired and stored by acting outside the blood-brain barrier. This assertion is supported by research on the behavioral effects of systemically administered enkephalins and opioid antagonists, the rapid hydrolysis of circulating enkephalins in vivo, and the limited ability of these peptides to penetrate the blood-brain barrier. A consideration of the extensive distribution of enkephalins throughout peripheral autonomic systems leads to the proposal that enkephalins may act to modulate learning and memory by altering peripheral autonomic function; autonomic afferents may then communicate with the memory trace in the CNS through a central modulatory pathway outlined herein. Evidence that some stressful experiences may lead to increases in circulating enkephalins also is discussed. The sites of action of these circulating enkephalins may involve peripheral autonomic sites, or additionally may involve the circum-ventricular organs. As a further regulatory mechanism, circulating enkephalin levels may be controlled by experience-dependent alterations of the activity of enzyme systems that participate in their breakdown. Finally, it is emphasized that the mechanisms of enkephalin action postulated herein may be applicable to the actions of other peripheral hormones, peptides, and neurotransmitters that participate in the modulation of learning and memory storage processes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245883
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  • 3
    Electronic Resource
    Electronic Resource
    Animal models of drug craving (1993)
    Springer
    Psychopharmacology 112 (1993), S. 163-182 
    Details
    ISSN: 1432-2072
    Keywords: Drug craving ; Addiction ; Drug dependence ; Incentive-motivation ; Animal models ; Validity ; Reliability ; Progressive ratio ; Choice ; Second-order schedule ; Extinction ; Conditioned reinforcement
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Drug craving, the desire to experience the effect(s) of a previously experienced psychoactive substance, has been hypothesized to contribute significantly to continued drug use and relapse after a period of abstinence in humans. In more theoretical terms, drug craving can be conceptualized within the framework of incentive motivational theories of behavior and be defined as the incentive motivation to self-administer a psychoactive substance. The incentive-motivational value of drugs is hypothesized to be determined by a continuous interaction between the hedonic rewarding properties of drugs (incentive) and the motivational state of the organism (organismic state). In drug-dependent individuals, the incentive-motivational value of drugs (i.e., drug craving) is greater compared to non-drug-dependent individuals due to the motivational state (i.e., withdrawal) developed with repeated drug administration. In this conceptual framework, animal models of drug craving would reflect two aspects of the incentive motivation to self-administer a psychoactive substance. One aspect would be the unconditioned incentive (reinforcing) value of the drug itself. The other aspect would be relatively independent of the direct (unconditioned) incentive value of the drug itself and could be reflected in the ability of previously neutral stimuli to acquire conditioned incentive properties that could elicit drug-seeking and drug-taking behavior. Animal models of drug craving that permit the investigation of the behavioral and neurobiological components of these two aspects of drug craving are reviewed and evaluated. The models reviewed are the progressive ratio, choice, extinction, conditioned reinforcement and second-order schedule paradigms. These animal models are evaluated according to two criteria that are established herein as necessary and sufficient criteria for the evaluation of animal models of human psychopathology: reliability and predictive validity. The development of animal models of drug craving will have heuristic value and allow a systematic investigation of the neurobiological mechanisms of craving.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244907
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  • 4
    Electronic Resource
    Electronic Resource
    Opiate withdrawal signs precipitated by naloxone following a single exposure to morphine: potentiation with a second morphine exposure (1997)
    Springer
    Psychopharmacology 129 (1997), S. 56-65 
    Details
    ISSN: 1432-2072
    Keywords: Key words Opiates ; Morphine ; Dependence ; Acute dependence ; Withdrawal ; Abstinence ; Naloxone
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies in humans with no prior history of opiate abuse indicated that naloxone-precipitated signs of opiate withdrawal could be observed after a single exposure to morphine, and that the severity of withdrawal was enhanced following a second morphine exposure 24 h later. The current study was conducted to establish a paradigm in rodents that resembled these conditions described in humans. To that end, naloxone-precipitated (0.03–3.0 mg/kg) suppression of operant response rates and somatic signs of withdrawal following single or repeated treatments with morphine (5.0 mg/kg) were assessed in previously opiate-naive rats. In one group of rats, naloxone was administered 4 h after both the first and second morphine pretreatment, while in a separate group of rats naloxone was administered 4h after the second morphine pretreatment only. A single morphine pretreatment significantly increased naloxone’s potency to suppress operant response rates, and resulted in the precipitation by naloxone of certain somatic signs of withdrawal. The effects of naloxone on both dependent measures (operant response rates and somatic signs) were potentiated following a second morphine pretreatment, regardless of whether naloxone was administered following both morphine exposures or only following the second morphine exposure. Thus, repeated morphine administration appears to be the critical factor underlying the progressive increase in antagonist potency, whereas prior experience with naloxone is not a necessary factor. The results provide additional support for the hypothesis that the development of dependence on opiates is a progressive phenomenon that may begin with a single dosing.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050162
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  • 5
    Electronic Resource
    Electronic Resource
    Corticotropin-releasing factor receptor blockade enhances conditioned aversive properties of cocaine in rats (1998)
    Springer
    Psychopharmacology 136 (1998), S. 247-255 
    Details
    ISSN: 1432-2072
    Keywords: Key words Corticotropin-releasing factor ; Cocaine ; Aversion ; Arousal ; Learning ; Runway ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioral profile of corticotropin-releasing factor (CRF) in mediating anxiogenic-like and aversive responses to stressors may be particularly relevant for dependence and withdrawal in drug-experienced organisms. Moreover, stressful aspects of drug exposure in the drug naive organism may also induce CRF system activation. In the present studies, the dependence of aversive properties of cocaine on activation of endogenous CRF systems has been evaluated in rats using taste conditioning and runway self-administration paradigms. Systemic cocaine administration (20 mg/kg IP) produced a conditioned saccharin aversion which was dose-dependently potentiated by central administration of the CRF receptor antagonist, D-phe CRF (12–41). In addition, IV cocaine administration (0.75 mg/kg per injection IV) produced runway goal-box avoidance and conditioned place avoidance responses which were significantly accelerated by CRF antagonist treatment. In contrast, CRF receptor stimulation using CRF itself abolished cocaine-induced increases in goal latency in the runway paradigm. This generalized involvement of CRF systems in cocaine-related motivational/associative states is consistent with the comprehensive role of CRF in mediating emotional responses to non-drug stressors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050563
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  • 6
    Electronic Resource
    Electronic Resource
    Heroin self-administration in dependent Wistar rats: increased sensitivity to naloxone (1999)
    Springer
    Psychopharmacology 144 (1999), S. 111-120 
    Details
    ISSN: 1432-2072
    Keywords: Key words Heroin ; Self-administration ; Dependence ; Naloxone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract   Rationale: Non-dependent and dependent opiate users appear to be driven by two distinct motivational factors: the primary reinforcing properties of the drug, and the negative reinforcing effects associated with relieving the negative affective component of opiate withdrawal in the dependent state. Objective: To investigate the motivational significance of opioid dependence on heroin self-administration (HSA) in rodents. Methods: Rats were trained to self-administer heroin intravenously (0.06 mg/kg per infusion; FR1), and opiate dependence was induced by subcutaneous implantation of two morphine (75 mg base) pellets.Rats in a non-dependent control group received placebo pellets. Three days after pellet implantation, HSA was resumed in daily 3-h sessions until baseline criteria were met and testing was conducted with subcutaneous injections of vehicle or naloxone (0, 0.003, 0.01, 0.03 mg/kg) 115 min into the session. Results: Morphine-dependent rats significantly increased HSA upon 0.01 mg/kg naloxone treatment, but decreased response rates at 0.03 mg/kg. Placebo pellet-implanted rats increased heroin intake at the 0.01 and 0.03 mg/kg doses. In a second experiment, the HSA session was shortened to 1 h and the training dose reduced to 0.03 mg/kg per infusion in new groups of animals. HSA in placebo pellet-implanted rats was increased only following the highest dose of the antagonist, while dependent rats were still affected by naloxone doses of 0.003–0.03 mg/kg. When subjected to a progressive-ratio schedule (experiment 3), breaking point values in dependent animals were 198% above baseline. Conclusions: The present study supports the hypothesis that dependence-induction by morphine-pellet implant in rats resulted in increased sensitivity to very small naloxone doses, as measured by changes in HSA. Taken together, these data suggest that opiate dependence, as measured by changes in sensitivity to naloxone, is a continuum which can contribute to the motivational state of drug-seeking.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050983
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  • 7
    Electronic Resource
    Electronic Resource
    ICI 174,864, a selective delta opioid antagonist, reverses the learning impairment produced by [leu]enkephalin (1990)
    Springer
    Psychopharmacology 101 (1990), S. 102-109 
    Details
    ISSN: 1432-2072
    Keywords: Learning ; [Leu]enkephalin ; ICI 174,864 ; Delta receptors ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of opioid delta receptors in the learning impairment produced by [leu]enkephalin (LE) in one-way active avoidance conditioning was investigated in mice. LE (30 and 100 µg/kg) impaired acquisition of the avoidance response, whereas ICI 174,864 (3.0 mg/kg), a selective delta opioid receptor antagonist, enhanced acquisition. The impairment produced by 100 µg/kg LE was completely reversed by 1.0 mg/kg ICI 174,864, a dose of the antagonist that by itself had no effect. Control studies provided evidence that the effects of ICI 174,864 and LE on conditioning cannot be explained by performance variables such as alterations in activity levels or footshock sensitivity. The results suggest that opioid delta receptors play an important role in the modulation of learning, and that the effects of LE on avoidance conditioning are mediated by delta receptors.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245798
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  • 8
    Electronic Resource
    Electronic Resource
    Roles ofδ andμ opioid receptors in mediating the effects of enkephalins on avoidance conditioning (1992)
    Springer
    Psychopharmacology 109 (1992), S. 157-162 
    Details
    ISSN: 1432-2072
    Keywords: Opioid peptides ; Opioid receptors ; Selective agonists ; Selective antagonists ; Mu receptor ; Delta receptor ; Active avoidance conditioning ; Learning ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects on one-way active avoidance conditioning of pre-training, systemic administration of the selective μ-receptor agonist [d-Ala2,N-Me-Phe4, Glyol]enkephalin (DAGO), and the selective μ-receptor antagonist (d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), were determined in Swiss-Webster mice. A low dose of DAGO (0.92 µg/kg) moderately enhanced avoidance acquisition, whereas a 100 µg/kg dose of CTOP more dramatically impaired acquisition. However, the avoidance-enhancing dose of DAGO significantly increased locomotor activity as measured in a separate group of mice in the avoidance chamber, and the avoidance-impairing dose of CTOP significantly decreased activity. Under these same training conditions, earlier studies (Schulteis et al. 1988; Schulteis and Martinez 1990) demonstrated that enkephalins impaired avoidance learning, and selectiveδ-receptor antagonists such as ICI 174,864 enhanced learning; in contrast to the present study, both of these effects were dissociated from performance effects such as alterations in locomotor activity. Taken together, the results suggested that the effects of enkephalins were mediated by theδ-, but not μ-, class of opioid receptor.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245494
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