Effect of a selective dopamine D1 agonist (ABT-431) on smoked cocaine self-administration in humans.
BACKGROUND
Data in laboratory animals suggest that D1 receptor agonists may have potential utility for the treatment of cocaine abuse.


OBJECTIVE
The effects of ABT-431, a selective agonist at the dopamine D1 receptor, on the reinforcing, cardiovascular and subjective effects of cocaine were investigated in humans.


METHODS
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 i.v.) 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 D1 agonists may have potential utility for the treatment of cocaine abuse.
Haney
M
M
Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. mh235@columbia.edu
Collins
E D
ED
Ward
A S
AS
Foltin
R W
RW
Fischman
M W
MW
D000280:Administration, Inhalation; D000328:Adult; D003042:Cocaine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D018491:Dopamine Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D011355:Prodrugs / Q000009:adverse effects / Q000627:therapeutic use*; D011725:Pyridines / Q000009:adverse effects / Q000627:therapeutic use*; D012646:Self Administration; D013764:Tetrahydronaphthalenes / Q000009:adverse effects / Q000627:therapeutic use*
D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D011355:Prodrugs; D011725:Pyridines; D013764:Tetrahydronaphthalenes; C095428:adrogolide hydrochloride; D003042:Cocaine