Self-administration of (+)-methamphetamine and (+)-pseudoephedrine, alone and combined, by rhesus monkeys

Abstract

(+)-Methamphetamine (MA) is an illicit psychostimulant that can be synthesized from the nonprescription nasal decongestant, (+)-pseudoephedrine (PE). While MA is widely abused, PE appears to have little or no abuse liability in currently available formulations. However, PE produces centrally-mediated dopaminergic effects that are linked to the reinforcing effects of MA and other illicit psychostimulants and has been reported to function as a positive reinforcer in non-human primates. There has yet to be an assessment of the relative reinforcing effects of MA and PE. Therefore, the current study compared the reinforcing potency and strength of MA and PE, alone and combined, in four rhesus monkeys that were allowed to self-administer MA (0.003-0.3 mg/kg/inj), PE (0.1-3.0 mg/kg/inj), or combinations of the two under a progressive-ratio schedule of reinforcement. (+)-Methamphetamine functioned as a positive reinforcer in a dose-dependent manner. (+)-Pseudoephedrine also functioned as a positive reinforcer, but was less potent than MA. There were no differences in maximum injections between MA, PE, or any of the combinations of the two. Dose-addition analysis and the interaction index indicated that combinations of PE and MA were either additive or sub-additive in their reinforcing effects. These results suggest that, while MA is a more potent reinforcer than PE, the two drugs are comparable in terms of reinforcing strength. However, MA and PE do not appear to interact in a manner that enhances their relative reinforcing effects.

Fig. 1

Dose-response functions for self-administration of methamphetamine (MA; bold solid line, solid circles), (+)-pseudoephedrine (PA; thin solid line, open circles) and MA mixed with various concentrations of PE (hatched lines) under a progressive-ratio schedule of reinforcement. The top four graphs represent the data for individual monkeys, identified by numbers on the graphs. Each point is the mean value for two test sessions at each dose or combination. The bottom graph represents the data averaged across all four monkeys. Vertical lines are the range (SEM).

Fig. 2

Maximum number of injections per session for methamphetamine (MA), (+)-pseudoephedrine (PE), or MA mixed with 0.1, 0.3, or 1.0 mg/kg PE, respectively, regardless of MA dose(s). Each bar is the mean value for four monkeys and vertical lines are the SEM.