title: Dopamine D3 receptor-preferring agonist enhances the subjective effects of cocaine in humans.
abstract: Pramipexole is a D3 dopamine receptor-preferring agonist indicated for the treatment of Parkinson disease. Studies associate pramipexole with pathological gambling and impulse control disorders suggesting a role for D3 receptors in reinforcement processes. Clinical studies showed pramipexole decreased cocaine craving and reversed central deficits in individuals with cocaine use disorder. Preclinical studies have shown acute administration of pramipexole increases cocaine's reinforcing effects whereas other reports suggest chronic pramipexole produces tolerance to cocaine. In a randomized, double-blind, placebo-controlled study we examined the impact of pramipexole treatment on the subjective effects produced by cocaine in volunteers with cocaine use disorder. Volunteers received pramipexole titrated up to 3.0mg/d or placebo over 15 days. Participants then received intravenous cocaine (0, 20 and 40mg) on day 15. Cardiovascular and subjective effects were obtained with visual analog scales at time points across the session. Pramipexole alone increased peak heart rate following saline and diastolic blood pressure following cocaine. Pramipexole produced upwards of two-fold increases in positive subjective effects ratings following cocaine. These results indicate that chronic D3 receptor activation increases the subjective effects of cocaine in humans. Caution should be used when prescribing pramipexole to patients that may also use cocaine.
authors.affiliation: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, & Michael E. DeBakey VA Medical Center, Houston, TX, USA. Electronic address: tnewton@bcm.edu.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Newton
authors.affiliation: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, & Michael E. DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Colin N
authors.initials: CN
authors.lastname: Haile
authors.affiliation: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, & Michael E. DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Mahoney
authors.affiliation: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, & Michael E. DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Shah
authors.affiliation: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, & Michael E. DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Verrico
authors.affiliation: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, & Michael E. DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: De La Garza
authors.affiliation: Baylor College of Medicine, Menninger Department of Psychiatry and Behavioral Sciences, & Michael E. DeBakey VA Medical Center, Houston, TX, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kosten
mesh_terms: D000328:Adult; D052160:Benzothiazoles / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077487:Pramipexole; D050637:Receptors, Dopamine D3 / Q000819:agonists*; D012054:Reinforcement, Psychology
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D050637:Receptors, Dopamine D3; D000077487:Pramipexole; D003042:Cocaine
keywords: Cocaine use disorder; Drug reinforcement; Drug reward; Peak effects; Stimulants; Substance use disorder