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 cocaineusing 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 pretreatments with either 0 or 15 mg oral d-amphetamine 2 hours 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 progressiveratio procedure relative to placebo pretreatment. These results indicate that acute d-amphetamine pretreatment does not increase stimulant self-administration.

The role of human drug self-administration procedures in the development of medications

“…The potential utility of self-administration procedures in human laboratory research has been examined in the context of the development and evaluation of pharmacotherapies for the treatment of various substance dependence disorders (e.g., O'Brien and Gardner, 2005;Rukstalis et al, 2005;Stoops et al, 2007). These studies are germane to abuse liability testing because they have been commonly employed to detect the ability of the putative pharmacotherapy (typically as a pretreatment) to reduce the abuse liability of the targeted drug of abuse.…”

Relationship between oral D-amphetamine self-administration and ratings of subjective effects

“…Data from three studies (Rush et al, 2001; Stoops et al, 2004; Stoops et al, 2007b) that used similar d -amphetamine self-administration procedures were included in the current retrospective analysis. The reinforcing effects of d -amphetamine (low dose [8 or 10 mg] and high dose [16 or 20 mg]) or placebo were assessed using a modified progressive-ratio schedule of reinforcement in each of these studies.…”

“…Participants were required to click the mouse 25 (Stoops et al, 2007b) or 50 times (Rush et al, 2001; Stoops et al, 2004) to earn the first capsule. To earn each additional capsule, the number of required responses doubled (e.g., 25, 50, 100, 200, 400, 800, 1600, 3200 [Stoops et al, 2007b]). If at any point the volunteer responded NO when asked if he or she wanted to work for a capsule the task was terminated.…”

“…In one study, each capsule contained 0 mg (placebo), 1.25 mg (10 mg, low dose), or 2.5 mg (20 mg, high dose) d -amphetamine (Rush et al, 2001). In the other two studies, each capsule contained 0 mg (placebo), 1 mg (8 mg, low dose), or 2 mg (16 mg, high dose) d -amphetamine (Stoops et al, 2004; Stoops et al, 2007b). Cornstarch or lactose was used as filler.…”

Effects of Potential Agonist-Replacement Therapies for Stimulant Dependence on Inhibitory Control in Cocaine Abusers

“…Second, there is evidence to suggest that agonist replacement therapies may prime or reinstate drug-taking behavior (7). However, results of one study from our laboratory suggest that d-amphetamine pretreatment does not alter subsequent d-amphetamine self-administration (8). Finally, treatment with agonist-replacement medications may impair inhibitory control.…”