Differential effects of amphetamine and related compounds on locomotor activity and metabolic rate in mice

Locomotor activity was measured by photobeam interruptions, and metabolic rate by the production of CO2 (as minute volume expired CO2, or VECO2) in mice. d-Amphetamine (0.3 to 10 mg/kg IP) increased locomotor activity in a dose-dependent manner while suppressing VECO2 over the same 72-min test period, compared to saline-injected controls. This phenomenon of divergent effects on locomotor activity and metabolic rate required central stimulation, as neither ammonium sulfate nor p-hydroxyamphetamine suppressed VECO2. Oxygen consumption was also suppressed by d-amphetamine, indicating that the suppression of VECO2 involved more than a change in respiratory quotient. When baseline activity rates were increased with running wheels, VECO2 and activity were both suppressed by d-amphetamine; VECO2 was suppressed by d-amphetamine more in exercising mice than in sedentary mice. Anorexigenic agents phenmetrazine, aminoxaphen, and fenfluramine, when administered in doses equimolar to maximally effective doses of d-amphetamine, did not consistently affect activity or VECO2. Evidence for mediation of the VECO2 response by corticosterone and endogenous opioid peptides was negative. Further work, with other mediators of the stress response, or with more complete dose-effect studies with anorexigenic compounds, may be necessary to explicate the mechanism of this counter-intuitive divergence of two measures of activity in mice.