Opposed stages of continuous amphetamine administration: parallel alterations in motor stereotypies and in vivo...

Rats pretreated with different regimens of chronic d-amphetamine (d-Amp) administration were injected 24 h after cessation of chronic d-Amp with either d-Amp (to test the degree to which it now elicited motor stereotypies) or with [3H]spiroperidol (to study in vivo accumulation in 7 brain regions). Rats pretreated with 28 daily injections of d-Amp subsequently evidenced heightened stereotypies to d-Amp whereas other rats pretreated with the same amount of d-Amp for 28 days using slow-release pellets showed decreased stereotypies to d-Amp. In neither of these chronic groups was spiroperidol accumulation altered. But the administration of d-Amp continuously over briefer periods induced large and phasic alterations in both d-Amp induced stereotypes and in spiroperidol accumulation. Rats given continuous d-Amp for 24 h, allowed a 24 h drug-free period, and then injected evidenced a large potentiation of both stereotypies and in vivo accumulation of spiroperidol in the caudate nucleus, whereas after 5 days of continuous d-Amp administration rats showed attenuated stereotypies and decreased [3H]spiroperidol accumulation in the caudate, accumbens, and substantia nigra. These results imply that brief periods of continuous d-Amp administration produce large and phasic changes in dopamine systems.