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  • 1
    ISSN: 1432-2072
    Keywords: Pentylenetetrazol ; Drug dependence ; Withdrawal ; Mecamylamine ; Discrimination ; Diazepam ; Nicotine ; Anxiety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats were trained on an FR10 schedule of food reinforcement to press one lever after pentylenetetrazol (PTZ), 20 mg/kg, IP, and an alternate lever after saline. After acute nicotine, 0.64 mg/kg, SC, 35% of the rats pressed the PTZ-lever. Diazepam, 5 mg/kg, IP, blocked the stimulus produced by PTZ, and mecamylamine, 5 mg/kg, IP, blocked the stimulus produced by nicotine. Training was then suspended and rats were treated with nicotine, at 8-h intervals, 0.64 mg/kg on the 1st day, and 1.25 mg/kg on subsequent days, for 21 days. To determine whether nicotine withdrawal substitutes for the stimulus produced by PTZ, rats were tested with saline at various times after chronic nicotine injections. Data from this part of the study were replicated in another group given nicotine for 15 days. Saline at 8 h after nicotine (five determinations each group) produced a small but stable degree of PTZ lever selection (35±4%). At 48 h after termination of nicotine treatment, the percentage of rats selecting the PTZ lever (50%) was greater than that in a control group tested after an equivalent period without training. The PTZ-like stimulus detected after chronic nicotine was not altered by mecamylamine, was additive with PTZ, and was blocked by diazepam. These data suggest that withdrawal from chronic nicotine produces a weak PTZ-like stimulus, which can be antagonized by an anxiolytic drug.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Genetic basis of substance abuse ; Inbred strains ; Cocaine ; Self-administration ; Progressive-ratio ; Restriction fragment length polymorphisms ; Rats ; D1 receptor ; D2 receptor ; Dopamine ; SCH 23390 ; Eticlopride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated the influence of genetics on extent of cocaine taking in rats that were self-administering cocaine under a progressive-ratio schedule. Fischer 344, ACI and Brown Norway rats were subjects because previous genetic studies on dopamine receptor loci have indicated that these are genetically divergent strains. All subjects were assessed for acquisition and stability of cocaine self-administration under a progressive-ratio schedule. Subsequently, a dose-effect curve for cocaine self-administration was determined for each strain. Fischer 344 rats maintained a higher average breaking point than did the ACI or Brown Norway strains. In addition, dopamine receptor antagonists differentially reduced the ability of cocaine to serve as a reinforcer across the three strains. The D1-selective dopamine receptor antagonist, SCH 23390, and the D2/D3-selective dopamine receptor antagonist, eticlopride, were significantly more effective in reducing the self-administration of cocaine in Brown Norway rats than for the other two strains. The results of this study demonstrate that genetic differences may play an important role in determining responding under progressive-ratio schedules for cocaine, possibly due to differences in the reinforcing efficacy of cocaine.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Genetic basis of substance abuse ; Inbred strains ; Cocaine ; Self-administration ; Progressive-ratio ; Restriction fragment length polymorphisms ; Rats ; D1 receptor ; D2 receptor ; Dopamine ; SCH 23390 ; Eticlopride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  This study investigated the influence of genetics on extent of cocaine taking in rats that were self-administering cocaine under a progressive-ratio schedule. Fischer 344, ACI and Brown Norway rats were subjects because previous genetic studies on dopamine receptor loci have indicated that these are genetically divergent strains. All subjects were assessed for acquisition and stability of cocaine self-administration under a progressive-ratio schedule. Subsequently, a dose-effect curve for cocaine self-administration was determined for each strain. Fischer 344 rats maintained a higher average breaking point than did the ACI or Brown Norway strains. In addition, dopamine receptor antagonists differentially reduced the ability of cocaine to serve as a reinforcer across the three strains. The D1-selective dopamine receptor antagonist, SCH 23390, and the D2/D3-selective dopamine receptor antagonist, eticlopride, were significantly more effective in reducing the self-administration of cocaine in Brown Norway rats than for the other two strains. The results of this study demonstrate that genetic differences may play an important role in determining responding under progressive-ratio schedules for cocaine, possibly due to differences in the reinforcing efficacy of cocaine.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 101 (1990), S. 292-309 
    ISSN: 1432-2072
    Keywords: Drugs of abuse ; Drug withdrawal ; Drug discrimination ; Discriminative stimulus ; Withdrawal signs ; Withdrawal symptoms ; Benzodiazepines ; Diazepam ; Ethanol ; Cocaine ; Anxiety ; Drug dependence
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract There have been few attempts to model subjective symptoms of drug withdrawal using animals as subjects. Two approaches for developing such models are reviewed. First, using drug discrimination methodology, it may be possible to train animals to detect the effects of withdrawal. This method has two difficulties: 1) the only discriminations trained to date involve precipitated withdrawal, and 2) the stimulus controlling behavior is difficult to specify. Second, withdrawal from many drugs of abuse produces the symptom of anxiety, and it seems likely that animal models of anxiety could be useful for studying drug withdrawal. This hypothesis has been explored most fully using subjects trained to detect the discriminative stimulus properties of the putative anxiogenic drug pentylenetetrazole (PTZ). Withdrawal from benzodiazepines or ethanol substitutes fully for PTZ, and withdrawal from cocaine, morphine, and nicotine substitutes partially for PTZ. Emerging data suggest that other animal models of anxiety may also be useful for detecting drug withdrawal. The final portion of this review examines a behavioral test that is very sensitive for detecting physical signs of withdrawal in animals. In subjects maintained on an operant baseline using food as a reinforcer, withdrawal from a drug of dependence frequently is associated with disruption of that operant behavior. For example, tetrahydrocannabinol and cocaine, drugs that are not traditionally seen as having significant withdrawal signs, produce disruption of operant responding when high-dose administration is terminated, and their readministration reverses this behavioral disruption. Based on the observation that withdrawal is associated with anxiogenic stimuli, we suggest a method to determine if disruption of operant behavior may be related to these stimuli.
    Type of Medium: Electronic Resource
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