The general aim of the research proposed in this application is to examine subjective and electrophysiological bases of stimulant drug preference. Using a laboratory-based preference procedure, we will select two groups of subjects: A stimulant-preferring group that chooses to self-administer d-amphetamine over placebo and a placebo-preferring group that has the reverse preference. The response to placebo and two doses of d-amphetamine will be assessed, in separate sessions, using a test battery comprising measures derived from the resting electroencephalogram (EEG), event-related brain potentials (ERPs) recorded during tests of auditory and visual sustained attention, auditory ERPs recorded during a combined oddball/novelty paradigm, standing stability and self-reports of subjective effects. The 55-minute battery will be administered once before and three times following d-amphetamine ingestion to permit drug effects to be analyzed over time. In two studies (Study I: N=50 males; Study II: N=50 females), drug response of individuals who choose to self-administer d-amphetamine (n=25) will be compared to that of individuals who choose not to self-administer d-amphetamine (n=25). The hypotheses are as follows: (1) Subjects preferring d-amphetamine will, in response to placebo, show subjective and electrophysiological changes over time consistent with diminished arousal (e.g., decreases in subjective ratings of arousal, increases in ratings of fatigue, increases in low-frequency of EEG activity and decrements in vigilance performance); (2) Subjects preferring d-amphetamine will show the following response to d-amphetamine: Increases in self-reports of arousal and EEG signs of increased activation, and more effective allocation of attention to stimuli. In addition, we will test the following hypotheses relevant to sex differences: (3) Using data from the preference-testing phase of the study, we will test the hypothesis that a greater proportion of females than males will prefer d-amphetamine over placebo. Based on animal studies of d-amphetamine effects, we hypothesize further that (4) females will exhibit more intense subjective and electrophysiological responses to d-amphetamine than males; and, based on previous human studies of drug preference, we predict that (5) the relationship between drug-preference and d-amphetamine response will be the same in males and females (i.e., that, in both sexes, preference for d-amphetamine over placebo will be associated with stimulant-like subjective and electrophysiological effects). The studies proposed in this application will examine relationships among individual differences in preference for d-amphetamine, baseline subjective and electrophysiological characteristics, and subjective and electrophysiological response to d-amphetamine. Accordingly, this research will link behavioral, subjective and electrophysiological data in analyses of individual differences in the effects of stimulant drugs.
| Gabbay, Frances H; Duncan, Connie C; McDonald, Craig G (2010) Brain potential indices of novelty processing are associated with preference for amphetamine. Exp Clin Psychopharmacol 18:470-88 |
| Gabbay, Frances H (2005) Family history of alcoholism and response to amphetamine: sex differences in the effect of risk. Alcohol Clin Exp Res 29:773-80 |
| Gabbay, Frances H (2003) Variations in affect following amphetamine and placebo: markers of stimulant drug preference. Exp Clin Psychopharmacol 11:91-101 |
