Day and night locomotor activity effects during administration of (+)-amphetamine.

Rats were given continuous subcutaneous amphetamine infusions (0, 2, 6, 10 and 20 mg/kg/day) via osmotic minipumps. The effects of these treatments on the locomotor activity of rats were determined over both light and dark phases of a 12-hr light/dark cycle for 336 consecutive hours. It was observed that tolerance to the locomotor stimulant actions of (+)-amphetamine is both dose- and light/dark cycle-dependent. Locomotor stimulation induced by the two highest doses remained high during both day and night throughout the period of treatment, except for the first few days and nights with the highest dose. Tolerance developed only to the effects of the two lower doses, and only during the day. Effects of the low doses on locomotor activity and on circadian patterns of locomotor activity are roughly similar to those previously observed with continuous administration of a selective dopamine D2 agonist. This behavioral similarity suggests that dopamine released by continuous administration of low doses of (+)-amphetamine may be producing its effects via selective actions on DA D2 receptors in vivo.