Intravenous (+)-methamphetamine causes complex dose-dependent physiologic changes in awake rats

Hemodynamic and temperature dose-response relationships were characterized in freely moving rats following i.v. (+)-methamphetamine administration to mimic the rapid onset of effects experienced by many human users. Rats received saline and (+)-methamphetamine in a repeated-measures, mixed-sequence design at 22+/-1 degrees C. Significantly greater blood pressure and heart rate elevations were observed after 1.0 and 3.0 mg/kg (+)-methamphetamine vs. 0.1 and 0.3 mg/kg. The time to peak hemodynamic values and the duration of effects were significantly greater after 3.0 mg/kg vs. the lower doses. The time to peak temperatures was significantly longer after 1.0 mg/kg vs. the lower doses. Following 3.0 mg/kg, all rats experienced temperature decreases before having elevated temperatures. The duration and magnitude of the delayed temperature elevations were significantly greater after 3.0 mg/kg vs. the lower doses. In conclusion, the (+)-methamphetamine-induced hemodynamic and temperature effects were not temporally synchronized, and the complex responses were not linearly related to dose.