A Comparison of Amphetamine- and Methamphetamine-induced Locomotor Activity in Rats: Evidence for Qualitative Differences in Behavior

Rationale: Methamphetamine (METH) is typically characterized as a more potent psychostimulant than amphetamine (AMPH), but few studies have directly compared the effects of these drugs at low, behaviorally activating doses that tend not to produce focused stereotypy.

Objectives: The objective of the study was to compare the effects of AMPH or METH treatment on locomotor activity in an open-field arena, focusing on their ability to produce conditioned locomotor activity, sensitization, and cross-sensitization.

Materials And Methods: Adult male rats were given AMPH or METH (0.5 or 1.0 mg/kg) for 5 days, with half of the rats presented with discrete, salient stimuli (S+) during the postinjection period. After a 3-day withdrawal, they were given three different injections on successive days: a saline challenge to assess conditioned responding, a drug challenge to assess sensitization, and a cross-sensitization test to the same dose of the drug with which they were not pretreated.

Results: Except in certain conditions, AMPH and METH were equipotent at activating locomotor activity. The exceptions included when rats were presented with S+ on acute and drug challenge days and in tests of cross-sensitization. There were no consistent differences in the magnitude of sensitization produced by AMPH or METH, and both drugs produced similar amounts of conditioned locomotion after a saline injection.

Conclusions: We have found specific conditions where METH is more potent than AMPH, but this study and others that used higher doses of these drugs are not consistent with the generalized characterization of METH as a more potent psychostimulant.