The present study was designed to examine the effect of pretreatment with amphetamine on the ability of amphetamine to release dopamine from slices of the nucleus accumbens and striatum and to stimulate locomotor activity or stereotyped behavior, after direct injection into either the nucleus accumbens or the striatum. Rats were injected twice daily for 5 days with either amphetamine (5 mg/kg, i.p.) or saline. At 33 days after this pretreatment, the release of endogenous dopamine from both regions of the brain in vitro by amphetamine and the changes in behavioral responses to the direct injection of amphetamine into either region were examined. Amphetamine at both 1 and 10 microM stimulated the release of endogenous dopamine from slices prepared from both of the brain areas. The release of dopamine by amphetamine was increased in rats pretreated with amphetamine. Consistent with its ability to stimulate endogenous release of dopamine, amphetamine, when injected into the nucleus accumbens, stimulated locomotor activity, while stereotyped behavior was enhanced when amphetamine was injected into the striatum. However, the locomotor activity and stereotyped behavioral responses to small doses of amphetamine (5, 10 or 25 micrograms) were not significantly greater in amphetamine-pretreated rats, compared to saline-pretreated animals. A greater stimulation of both responses in amphetamine-pretreated rats was only observed when a large dose (50 micrograms) of amphetamine was administered into either the nucleus accumbens or striatum.(ABSTRACT TRUNCATED AT 250 WORDS)