title: Modulating tobacco smoking rates by dopaminergic stimulation and blockade.
abstract: This study was designed to demonstrate that dopaminergic stimulation would result in decreased smoking behavior and nicotine intake, whereas dopaminergic blockade would result in increased smoking behavior and nicotine intake, in the same subjects. In prior human studies, a dopaminergic antagonist, haloperidol, increased smoking and/or nicotine intake, and a dopamine agonist, bromocriptine, decreased smoking. The smoking behavior of 20 heavy smokers was observed on two separate visits in a randomized, double-blind, repeated-measures-within-subject design. In the drug-reversal design, either bromocriptine (2.5 mg) or haloperidol (2.0 mg) was administered at each 5-h session, during which subjects smoked their own cigarettes ad libitum. Smoking topography was measured using a thermistor flow detector apparatus. Subjects smoked their cigarettes faster (p<0.05) and total puffing time was greater (p<0.05) with haloperidol than with bromocriptine. There was a trend for both a shorter latency to smoke (p<0.10, one-tailed) during time of expected peak drug concentration and for a shorter inter-cigarette interval with haloperidol than with bromocriptine (p<0.10, one-tailed). Shiffman-Jarvik Withdrawal Scale craving subscale scores increased significantly more with haloperidol than with bromocriptine (p<0.05). Mean Profile of Mood States (POMS) scores differed significantly for only one subscale (Confusion: bromocriptine>haloperidol; p<0.05). These data support the hypothesis that nicotine mediates reinforcement from smoking via dopamine, and that smoking behavior can be manipulated within the same subjects in opposite directions by alternately stimulating and blocking dopamine.
authors.affiliation: University of California Los Angeles School of Medicine and VA West Los Angeles Healthcare Center, VA Greater L.A. Healthcare System, Los Angeles, CA 90073, USA. nhcaskey@ucla.edu
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: Caskey
authors.forename: Murray E
authors.initials: ME
authors.lastname: Jarvik
authors.forename: William C
authors.initials: WC
authors.lastname: Wirshing
authors.forename: Damian C
authors.initials: DC
authors.lastname: Madsen
authors.forename: Paula N
authors.initials: PN
authors.lastname: Iwamoto-Schaap
authors.forename: Naomi I
authors.initials: NI
authors.lastname: Eisenberger
authors.forename: Lorena
authors.initials: L
authors.lastname: Huerta
authors.forename: Scott M
authors.initials: SM
authors.lastname: Terrace
authors.forename: Richard E
authors.initials: RE
authors.lastname: Olmstead
mesh_terms: D000293:Adolescent; D000328:Adult; D001944:Breath Tests; D001971:Bromocriptine / Q000627:therapeutic use*; D002245:Carbon Dioxide / Q000032:analysis; D003367:Cotinine / Q000097:blood; D018492:Dopamine Antagonists / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000097:blood; D011795:Surveys and Questionnaires; D014029:Tobacco Use Disorder / Q000453:epidemiology / Q000517:prevention & control*
chemical_list: D018492:Dopamine Antagonists; D002245:Carbon Dioxide; D001971:Bromocriptine; D009538:Nicotine; D006220:Haloperidol; D003367:Cotinine