To test the effects of systemic and local amphetamine on dopamine and serotonin release in freely moving rats, guide cannulas were implanted in the nucleus accumbens and ventral striatum for removable 200 mu microdialysis probes. Comparing 45 min samples before and after IP amphetamine (2 mg/kg), dopamine (DA) in dialysate from the accumbens increased from a baseline of 3 pg/20 microliters to 11 pg/20 microliters whereas dopamine metabolites, DOPAC and HVA decreased. This was probably due to block of DA reuptake and inhibition of monoamine oxidase, MAO. Accumbens serotonin increased from a baseline of 8 to 11 pg/20 microliters. Changes in the ventral striatum were similar. In the second experiment, microdialysis was performed before and after local injection of amphetamine (4 micrograms) to reveal effects of amphetamine in the terminal area only instead of the whole brain. DA in the accumbens increased from 11 to 147 pg per sample; serotonin, from 11 to 107. The effect was even larger in the ventral striatum. DA increased from 12 to 409 pg/20 microliters; serotonin, 3 to 139. To avoid handling the rat or disturbing brain tissue in experiment three, amphetamine was infused via the microdialysis probe during ongoing dialysis sampling. Perfusate containing amphetamine was switched into the flow line which allowed roughly 10% or 4 micrograms to diffuse out into the extracellular space. During this 20 min, extracellular DA in the accumbens increased from a baseline of 10 pg/20 microliters to 300 pg/20 microliters sample. Serotonin increased from barely detectable to 60 pg/20 microliters. DOPAC decreased significantly; HVA and 5HIAA drifted lower.(ABSTRACT TRUNCATED AT 250 WORDS)