Association of Altered Whole-Body Metabolism with Locomotor Sensitization Induced by Quinpirole

Repeated exposure to drugs classed as psychostimulants can produce behavioral sensitization, defined as augmented motor responses to fixed doses of such compounds. For example, chronic treatment of rats with the dopamine D2/D3 agonist quinpirole increases the locomotor response to this drug to levels that are several times higher than after acute treatment. To determine if such enhanced activity is associated with changes in energy metabolism, one group of rats (n = 16) received 11 injections of quinpirole (0.5 mg/kg every second day) while a second received equal numbers of saline injections. Immediately after each injection, rats were placed in individual metabolic chambers where oxygen (O2) consumption, carbon dioxide (CO2) output, and motor activity were measured every 5 min for the next 2 h. Locomotor responses to quinpirole doubled during the course of treatment, thereby confirming the establishment of behavioral sensitization. The magnitude of energy metabolism and motor activity were positively correlated in control rats but not in quinpirole-treated rats. However, quinpirole reliably reduced respiratory quotient (CO2/O2). This suggests that enhanced utilization of body lipids could be a separate physiological consequence of quinpirole that might support in part the heightened locomotor activity characteristic of the behavioral sensitization it induces.