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  • 1
    ISSN: 1432-2072
    Keywords: Key words Nicotine ; Self-administration ; Progressive ratio ; Rodents ; Reinforcement ; Extinction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Robust intravenous (i.v.) nicotine self-administration (SA) in rats has been reported by several laboratories, including our own, using fixed ratio (FR) schedules of reinforcement. Studies on other drugs of abuse, however, suggest that progressive ratio (PR) schedules may provide additional information not gained using FR schedules. Objective: Here, we attempt to establish and characterize nicotine SA on a PR. Methods: One study allowed animals to acquire SA on a FR at four doses of nicotine (0.02, 0.03, 0.06, 0.09 mg/kg) before being switched to a PR. A second study examined extinction by saline substitution or pretreatment with the nicotinic antagonist, mecamylamine, including a preliminary analysis into the role of secondary reinforcers in the extinction process. Results: SA of nicotine on a PR was stable across repeated sessions. The number of infusions earned on a PR correlated with infusion rate on a FR; however, a large portion of the variance in SA on a PR could not be accounted for by infusion rate on a FR. Infusions on a PR increased across the same range of doses that produced a decrease in the infusion rate on a FR. Extinction of responding occurred after saline substitution or pretreatment with mecamylamine, and animals re-acquired when nicotine was again available without pretreatment. The presence of drug-paired stimuli appeared to lengthen the extinction process. Conclusions: Nicotine supports stable SA on a PR. Since PR and FR schedules may measure different aspects of nicotine reinforcement, PR schedules may be valuable in further characterizing group and individual differences in nicotine reinforcement.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Olanzapine ; Clozapine ; Chlorpromazine ; Haloperidol ; Thioridazine ; Raclopride ; Risperidone ; Scopolamine ; Ritanserin ; Atypical antipsychotic ; Neuroleptic ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Rationale: Analysis of the preclinical behavioral effects of atypical antipsychotic agents will provide a better understanding of how they differ from typical antipsychotics and aid in the development of future atypical antipsychotic drugs. Objectives: The present study was designed to provide information about the discriminative stimulus properties of the atypical antipsychotic olanzapine. Methods: Rats were trained to discriminate the atypical antipsychotic olanzapine (either 0.5 mg/kg OLZ or 0.25 mg/kg OLZ, i.p.) from vehicle in a two- lever drug discrimination procedure. The atypical antipsychotic clozapine fully substituted for olanzapine in both the 0.5-mg/kg OLZ group (99.3% drug lever responding [DLR]) and the 0.25-mg/kg OLZ group (99.9% DLR). The typical antipsychotic chlorpromazine also substituted for olanzapine in both the 0.5-mg/kg OLZ group (87.5% DLR) and in the 0.25-mg/kg OLZ group (98.9% DLR); whereas, haloperidol displayed partial substitution for olanzapine in the 0.5-mg/kg OLZ group (56.1% DLR) and in the 0.25-mg/kg OLZ group (76.4% DLR). The 5.0-mg/kg dose of thioridazine produced olanzapine-appropriate responding in the 0.5-mg/kg OLZ group (99.6% DLR), but only partial substitution was seen with the 0.25-mg/kg OLZ training dose (64.0% DLR). The atypical antipsychotics raclopride (53.9% DLR) and risperidone (60.1% DLR) displayed only partial substitution in the 0.5-mg/kg OLZ group. Both the muscarinic cholinergic antagonist scopolamine (90.0% DLR) and the 5-HT2A/2C serotonergic antagonist ritanserin (86.0% DLR) fully substituted for olanzapine in the 0.5-mg/kg OLZ group. Conclusions: In contrast to previous discrimination studies with clozapine-trained rats, the typical antipsychotic agents chlorpromazine and thioridazine and the serotonin antagonist ritanserin substituted for olanzapine. These results demonstrate that there are differences in the mechanisms underlying the discriminative stimulus properties of clozapine and olanzapine. Specifically, olanzapine’s discriminative stimulus properties appear to be meditated in part by both cholinergic and serotonergic mechanisms.
    Type of Medium: Electronic Resource
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