Sequential changes in behavior induced by continuous infusions of amphetamine in rats.

Rats infused with amphetamine (0.65 mg/kg/h) for 5 days through Alzet (Tm) minipumps displayed a multiphasic sequence of behavioral changes. The behavior of the animals was characterized during daily 40-min test sessions in behavioral pattern monitors (BPM). Within 24 h after implantation of the minipumps, rats infused with amphetamine exhibited prolonged periods of oral stereotypies (licking or biting). By the 3rd day this stereotypy was replaced with locomotor and investigatory activation as the predominant response pattern. In addition, the magnitudes of tactile startle responses were reduced in a separate group of animals infused with amphetamine for 9 days. In accord with previous findings, dopamine (DA) in the corpus striatum was markedly reduced by the 3rd day, whereas DA in the nucleus accumbens was transiently increased. These results indicate that continuous infusion of amphetamine produces a relatively selective depletion of striatal DA resulting in a reduction in amphetamine-induced stereotypy with a corresponding increase in locomotor activation.