Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self administration in humans

Rationale: Data in laboratory animals suggest that D-1 receptor agonists may 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 the reinforcing, cardiovascular and subjective effects of cocaine were investigated in humans. Method: Nine experienced cocaine smokers (8M, 1F), participated 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 combination with three doses of smoked cocaine (0, 12, 50 mg). ABT-431 was intravenously administered over a 1-h period immediately prior to cocaine self-administration sessions. A six-trial choice procedure (cocaine versus $5 merchandise vouchers) was utilized, with sessions consisting of: (a) one sample trial, where participants received the cocaine dose available that day, and (b) five choice trials, where participants chose between the available cocaine dose and one merchandise voucher. Results: ABT-431 did not affect 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 for ABT-431 (4 mg) to decrease cocaine craving. ABT-431 also increased heart rate, while decreasing systolic and diastolic pressure at each dose of cocaine. Conclusions: These data suggest that D-1 agonists may have potential utility for the treatment of cocaine abuse.