Long-term administration of d-amphetamine: Progressive augmentation of motor activity and stereotypy

TLDR: carry-over of both the post-injection augmentation and dark phase reduction of locomotion was revealed during amphetamine retest 8 days following discontinuation of daily d-amphetamine injections, indicating the importance of their concurrent evaluation, especially during chronic studies.

Abstract: The competitive relationship between d-amphetamine induced stereotypy and locomotor activity indicates the importance of their concurrent evaluation, especially during chronic studies. Repeated injection of 0.5, 1.0, 2.5, 5.0, or 7.5 mg/kg d-amphetamine for 36 successive days, in rats continuously exposed to the experimental chambers, produced a progressive augmentation in stereotypy and/or locomotion (depending on dose) during the 3–4 hr interval following injections (post-injection phase). In contrast, dark phase locomotor activity (8–20 hr after each daily injection) was maximally reduced (30–40% of controls) after the first injection of either 5.0 or 7.5 mg/kg d-amphetamine and gradually declined to this level with repeated injection of 1.0 and 2.5 mg/kg. Carry-over of both the post-injection augmentation and dark phase reduction of locomotion was revealed during amphetamine retest 8 days following discontinuation of daily d-amphetamine injections. Possible mechanisms underlying these behavioral alterations are discussed.