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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 98 (1989), S. 61-67 
    ISSN: 1432-2072
    Keywords: Rat ; Place preference ; Extinction ; Conditioning ; Naloxone ; Heroin ; Clonidine ; Pimozide ; Memory
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These experiments examined the neurochemical mechanisms involved in the development and expression of place conditioning produced by heroin. Conditioned place preferences (CPP) lasting up to 8 weeks were obtained with doses of 50–1000 μg/kg heroin, using a regimen shown not to produce physical dependence. Naloxone pretreatment (50 μg/kg) during conditioning prevented the acquisition of heroin-induced CPP, but when given only on the test day, naloxone (50 or 1000 μg/kg) did not prevent the expression of heroin CPP. Clonidine disrupted the establishment of heroin CPP at 20 μg/kg, but disrupted its expression only at debilitating doses (100 and 200 μg/kg). Pimozide attenuated the acquisition (100 μ/kg) and expression (250 μg/kg) of heroin CPP. Together, these results support a role for opioid and catecholamine systems in the acquisition of heroin reinforcement, but they suggest that once heroin CPP is established, its expression in opiate-free subjects is not opiate receptor mediated and is relatively refractory to pharmacological treatments which disrupt acquisition. The data challenge the notion that the conditioned effects of opiates in drug-free animals are related to the release of endogenous opioids, and they also may help to explain why naloxone and clonidine are ineffective in the treatment of opiate addiction.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Arylpiperazine ; Serotonin1A ; Operant behavior ; Waiting capacity ; Antidepressant ; Anxiolytic ; Interresponse times
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of four serotonin (5-HT)-1A compounds (buspirone, gepirone, ipsapirone and zalospirone) were compared with 5-hydroxytryptophan (5-HTP) [a 5-HT precursor with antidepressant (AD) efficacy], and diazepam (a benzodiazepine anxiolytic), on a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule. Past research has shown that AD and anxiolytic compounds each have distinct effects on the DRL 72-s interresponse time (IRT) distribution profile. In the present paper, the profile of the IRT distribution was quantitatively characterized by three metrics: burst ratio, peak location and peak area. 5-HTP shifted the IRT distribution peak toward longer IRT durations, increased reinforcement rate and decreased response rate. The profile of the IRT distribution was not disrupted by 5-HTP. Diazepam disrupted the IRT distribution and increased bursting. In general, the arylpiperazine, 5-HT1A compounds increased reinforcement rate, decreased response rate and disrupted the profile of the IRT distribution. The effects of the four arylpiperazine 5-HT1A compounds on the IRT distribution profile were different from the AD profile of 5-HTP and the benzodiazepine anxiolytic profile of diazepam. Disruption of the IRT distribution by buspirone, gepirone, ipsapirone and zalospirone may result from decreased 5-HT transmission mediated by the presynaptic, somatodendritic 5-HT1A receptor.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 88 (1986), S. 472-479 
    ISSN: 1432-2072
    Keywords: Opiates ; Morphine ; Naloxone ; Self-stimulation ; Reinforcement ; Dopamine ; Sensitization ; Conditioning ; Tolerance
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract These experiments tested the hypothesis that the suppressing and facilitating effects of morphine on intracranial self-stimulation (ICS) (measured 1 h and 3 h post-injection, respectively) are influenced by associative, non-pharmacological factors. Experiment 1 confirmed previous demonstrations that the facilitation of ICS by morphine (10 mg/kg) develops with repeated drug exposures. Once ICS facilitation had developed, the effect was mimicked by saline injection in most subjects. In a separate group of animals, previous exposure to morphine in the home cage prevented drug-induced facilitation of ICS. Tolerance to ICS suppression developed after repeated pairings of the drug and the ICS chambers, but not when the drug had previously been received in the home cage. Experiment 2 examined the effect of low (0.3, 1, 3 mg/kg) doses of chronic morphine on ICS. Facilitation was observed with 1 and 3 mg/kg, but only after repeated testing. Naloxone (0.1 and 1 mg/kg) failed to reverse facilitation in a number of these subjects. In Experiment 3, animals receiving their daily injections of morphine were allowed to self-stimulate only at 3 h post-injection (when ICS facilitation is usually maximal), rather than at 1 h and 3 h post-injection. ICS facilitation was not observed, even with repeated testing. These data indicate that the facilitation of ICS by morphine is the outcome of a learned association between drug administration and the ICS procedure, rather than the invariable result of opiate receptor activation. Repeated exposure to morphine is required for the initial establishment of ICS enhancement, but the subsequent expression of this behavior is not directly related to opiate receptor activity.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Mianserin ; Atypical antidepressants ; DRL 72-s schedule ; Serotonin ; 5-HT2 receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioral effects of racemic mianserin, its (+) and (−) enantiomers, and its metabolites desmethylmianserin and 8-hydroxymianserin were evaluated on the differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule, a screen known to be sensitive to and specific for the antidepressant properties of drugs. Racemic mianserin produced the antidepressant-like effect (increased reinforcement rate, decreased response rate) at 5 and 10 mg/kg. The mianserin enantiomers showed the antidepressant-like effect beginning at lower doses [(+) mianserin; 0.6 mg/kg; (−) mianserin: 2.5 mg/kg]. The mianserin metabolites showed no clear dose-related effect at doses up to 10 mg/kg. It is concluded that the antidepressant-like effects of mianserin are due to the activity of the parent compound rather than to its metabolites, and that they may be primarily attributable to the (+) enantiomer. The greater potency of (+)-mianserin may be related to its higher affinity for the 5-HT2 receptor.
    Type of Medium: Electronic Resource
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