Pharmacological regulation of intravenous cocaine and heroin self-administration in rats: a variable dose paradigm

Rats were trained to intravenously self-administer unit doses of cocaine or heroin. Constant supplemental infusion of a portion of each rat's mean hourly intake increased the mean time between successive infusions, but the effect was not statistically reliable from the data of a small sample of animals. A variable dose per infusion (VDI) paradigm was developed which enabled testing of several unit doses of cocaine or heroin within single test sessions. Unit doses of 0.5, 1.0, and 2.0 mg/kg of cocaine or 0.025, 0.05, and 0.1 mg/kg of heroin were made available with equal frequency but in unpredictable sequence to independent groups of rats. The mean time between successive infusions was linearly related to the log dose of the preceding infusion in each case. Pimozide, a drug thought to attenuate the reinforcing effects of both cocaine and heroin, shifted the functions without disturbing the dose-response relations; pimozide reliably decreased the time between successive cocaine infusions across a 4-fold range of pimozide doses. The effect of pimozide on heroin self-administration was not statistically significant and disrupted responding at the highest dose tested. This paradigm thus offers a within-session assessment of the dose-dependent duration of reinforcing actions of cocaine and heroin, and this assessment is sensitive to at least one challenge of intravenous drug reinforcement.