Effect of a selective dopamine D-1 agonist (ABT-431) on smoked cocaine self administration in humans

Rationale: Data in laboratory animals suggest that D-1 receptor agonists ma y have potential utility for the treatment of cocaine abuse. Objective: The effects of ABT-431, a selective agonist at the dopamine D-1 receptor, on t he reinforcing, cardiovascular and subjective effects of cocaine were inves tigated in humans. Method: Nine experienced cocaine smokers (8M, 1F), parti cipated in nine self-administration sessions while residing on an inpatient research unit: three doses of ABT-431 (0, 2, 4 mg IV) were each given in c ombination with three doses of smoked cocaine (0, 12, 50 mg). ABT-431 was i ntravenously administered over a 1-h period immediately prior to cocaine se lf-administration sessions. A six-trial choice procedure (cocaine versus $5 merchandise vouchers) was utilized, with sessions consisting of: (a) one s ample trial, where participants received the cocaine dose available that da y, and (b) five choice trials, where participants chose between the availab le cocaine dose and one merchandise voucher. Results: ABT-431 did not affec t the number of times participants chose to smoke each dose of cocaine, but produced significant dose-dependent decreases in the subjective effects of cocaine, including ratings of "High," "Stimulated," dose liking, estimates of dose value, "Quality," and "Potency." Furthermore, there was a trend fo r ABT-431 (4 mg) to decrease cocaine craving. ABT-431 also increased heart rate, while decreasing systolic and diastolic pressure at each dose of coca ine. Conclusions: These data suggest that D-1 agonists may have potential u tility for the treatment of cocaine abuse.