Parallel role for the dopamine D1 receptor in gambling and amphetamine reinforcement in healthy volunteers

This study investigated the role of dopamine, and specifically the D1 receptor (D1R), in the reinforcing effects of a slot-machine game in healthy volunteers ( n=30). To compare gambling and drug effects, subjects received the prototypic psychostimulant drug d-amphetamine (AMPH; 20 mg) in a multi-session, placebo-controlled design. To isolate D1R, half the subjects were pretreated with the preferential D2 receptor antagonist haloperidol (HAL; 3 mg), and the other half with the mixed D1–D2 antagonist fluphenazine (FLU; 3 mg) before the game (Phase I) and AMPH (Phase II). HAL decreased and FLU increased the post-game desire to gamble and post-AMPH desire to take AMPH again, as well as amphetamine scale ratings on the Addiction Research Center Inventory after gambling and AMPH. The effects of the antagonists on desire to gamble and to take AMPH again were significantly intercorrelated. HAL increased and FLU decreased the salience of negative affective words on a rapid reading task after both reinforcers. HAL also decreased the salience of gambling words after AMPH. Both reinforcers increased diastolic blood pressure equally under antagonists and placebo. Results indicate that D1R plays a parallel role in the psychostimulant-like, incentive-motivational, and salience-enhancing effects of gambling and AMPH. Moderate D1R activation appears to optimize these effects in healthy subjects.

Subjective effects of modafinil, a new central adrenergic stimulant in healthy volunteers: a comparison with amphetamine, caffeine and placebo

SummaryThe subjective, behavioral and physiological effects of modafinil (300 mg PO) a new central adrenergic stimulant, were compared with those of dextroamphetamine (15 mg PO), caffeine (300 mg PO) and placebo in a randomized double-blind cross-over study. Sixteen healthy volunteers participated in the study y: 8 males and 8 females with no history of drug abuse and moderate use of caffeine. Subjective and behavioral effects were studied using the Addiction Research Center Inventory (ARCI), Profile of Mood States (POMS) and Visual Analog Scales before and 1, 2, 4 and 8 h post single oral dosing. Results showed that subjective effects of modafinil (300 mg) differed markedly from those of dextroamphetamine (15 mg). They were close to those produced by caffeine (300 mg). These results indicate that modafinil (300 mg) does not possess amphetamine-like subjective effects in a healthy population. If subjective feelings are related to drug abuse liability, it could be assumed that modafinil, at the dose used in therapeutics, does not possess any abuse liability comparable to amphetamine.