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  • Title: Tolerance to response-disruptive effects of cocaine is facilitated by opportunity to respond in the absence of drug.
    Author: Miller ML, Branch MN.
    Journal: Pharmacol Biochem Behav; 2004 Sep; 79(1):43-54. PubMed ID: 15388283.
    Abstract:
    A dose of cocaine that was 1/8 of a logarithmic unit larger than the smallest dose that produced complete suppression of responding of pigeons under a fixed-ratio 20 schedule was administered prior to 50 daily sessions. If responding occurred, then the dose was increased by 1/8 of a logarithmic unit and administered for an additional 50 sessions. The pigeons were divided into either a 'control' or 'saline' group. Control group pigeons received the same dose of cocaine for 100 additional days. Pigeons in the saline group were also exposed to a daily dosing regimen for 100 more sessions except that saline was substituted once every 5 days. Daily dosing then continued and dose-response functions were re-determined by substituting other doses for the daily dose every fifth session. During the first exposure to each dose, tolerance was evident for five of six pigeons in the saline group, whereas sensitization was evident for pigeons in the control group. Tolerance was observed in both groups following subsequent exposures. Tolerance to effects of behaviorally large doses of cocaine was therefore promoted when saline was occasionally substituted for the daily dose. Opportunity to respond during an ongoing regimen of daily cocaine administration enhanced the development of tolerance.
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