Acute d-amphetamine pretreatment does not alter stimulant self-administration in humans

Abstract

Recent clinical research indicates that d-amphetamine is effective in treating cocaine and methamphetamine dependence. There is concern, however, with the use of d-amphetamine as a pharmacotherapy because acute administration of d-amphetamine decreases inhibition in cocaine-using individuals and may increase drug-taking behavior. The purpose of the present experiment was to determine whether acute d-amphetamine pretreatment would alter the reinforcing, subject-rated, and cardiovascular effects of d-amphetamine. To this end, 7 human volunteers first sampled doses of oral d-amphetamine (0, 8, and 16 mg). These doses engender moderate drug taking and were selected to avoid a ceiling or floor effect. Volunteers were then allowed to self-administer these sampled doses using a modified progressive-ratio procedure in two sessions in which they received pretreatment with either 0 or 15 mg oral d-amphetamine 2 h prior to completing the modified progressive-ratio procedure. d-Amphetamine produced prototypical stimulant-like effects (e.g., increased ratings of stimulated, elevated blood pressure) and maintained responding on the modified progressive-ratio schedule. Pretreatment with 15 mg oral d-amphetamine also produced prototypical stimulant-like effects, but failed to alter break points for d-amphetamine on the modified progressive-ratio procedure relative to placebo pretreatment. These results indicate that acute d-amphetamine pretreatment does not increase stimulant self-administration.

Figure 1

Dose-response function for d-amphetamine for number of capsules earned on the Modified Progressive-Ratio Procedure as a function of pretreatment condition. X-axis: total d-amphetamine dose (mg). The dose per capsule was 0 mg d-amphetamine (placebo [PL]), 1 mg d-amphetamine (8 mg dose) and 2 mg d-amphetamine (16 mg dose). The maximum number of capsules earned was 8. Brackets indicate one S.E.M. Unidirectional brackets were used for clarity.

Figure 2

Dose- and Time-response functions for sampling doses of d-amphetamine for scores on the BG, MBG, and PCAG scales of the ARCI and subject ratings of Active/Alert/Energetic, Any Effect, Like Drug, Good Effects, Stimulated and Willing to Take Again from the Drug-Effect Questionnaire during Sampling Sessions. X-axis: hours following drug administration. The maximum score on the subject-rated measures was 4. Filled symbols are significantly different from placebo at that time point. Brackets indicate one S.E.M.

Figure 3

Dose- and Time-response functions for pretreatment doses of d-amphetamine for scores on the BG, MBG, and PCAG scales of the ARCI and subject ratings of Active/Alert/Energetic, Any Effect, Like Drug, Good Effects, Stimulated and Willing to Take Again from the Drug-Effect Questionnaire following administration of the pretreatment dose during Self-Administration Sessions. X-axis: hours following drug administration. The maximum score on the subject-rated measures was 4. Filled symbols are significantly different from placebo at that time point. Brackets indicate one S.E.M.