Psychomotor stimulant abuse represents a major component of the nation's drug abuse problem. Besides the drugs already available, new compounds with stimulant properties are being developed for various clinical applications. Given the established abuse liability of many stimulants, and apparent species differences in abuse liability, it is important to screen new compounds for their abuse liability in human subjects. The purpose of this proposal is to develop and test a new paradigm for assessing the reinforcing effects of psychomotor stimulants in normal human volunteers. The studies use a drug self-administration procedure which is a modification of a discrete trial choice procedure currently in use. The new protocol incorporates a non-drug choice option which will allow study of the effects of manipulating alternative reinforcers on drug self-administration. The paradigm will be tested for validity and sensitivity in a series of studies in which d-amphetamine serves as the prototype psychomotor stimulant of established abuse potential. One of these studies will investigate the effect of sleep deprivation on the reinforcing and subjective effects of amphetamine. Another study will attempt to demonstrate that increasing the value of an alternative reinforcer will decrease choice of amphetamine. The specificity of the paradigm will be examined by testing two other stimulants-ephedrine and methylphenidate-and comparing their reinforcing effects to those of amphetamine. The proposed studies should be particularly suitable for examining individual differences in the reinforcing effects of these drugs, and determining the bases for these differences by relating other variables (such as baseline mood state, personality traits, and physiological and behavioral indices of CNS arousal, noradrenergic and dopaminergic activity) to drug choice. Such variables may provide predictors of human psychomotor stimulant self-administration.
