Differential action of (+)‐amphetamine on electrically evoked dopamine overflow in rat brain slices containing corpus striatum and nucleus accumbens

Abstract

The effects of (+)‐amphetamine on electrically evoked dopamine overflow were examined in the rat brain slice containing either anterior caudate putamen (aCPu) or nucleus accumbens (NAc), by fast cyclic voltammetry. (+)‐Amphetamine (1 μm) caused a time‐dependent increase in the extracellular concentration of dopamine ([dopamine]ex) due to displacement of dopamine from terminal sites. After a 40 min superfusion, [dopamine]ex in the aCPu was 0.617 ± 0.117 μm and in the NAc was 0.270 ± 0.04 μm. Pretreatment with (–)‐sulpiride (1 μm) did not affect this action of (+)‐amphetamine. (+)‐Amphetamine (1 μm) exhibited a complex and time‐dependent effect on electrically stimulated dopamine overflow, evoked by 1p, 4p/10 Hz and 20p/20 Hz. In the aCPu, (+)‐amphetamine (1 μm) resulted in attenuation of dopamine overflow due to 1p and 4p/10 Hz but potentiation of dopamine overflow to 20p/20 Hz. (–)‐Sulpiride (1 μm) prior to (+)‐amphetamine (1 μm) reversed the attenuation of dopamine overflow evoked by 1p and 4p/10 Hz but had no significant effect on dopamine overflow evoked by 20p/20 Hz. (+)‐Amphetamine (1 μm) potentiated dopamine overflow in the NAc to all three stimuli. (–)‐Sulpiride (1 μm) prior to (+)‐amphetamine (1 μm), resulted initially, in a further potentiation of overflow, followed by a time‐dependent attenuation of dopamine overflow to all three stimuli. t1/2, the rate of removal of [dopamine]ex following electrical stimulation was not significantly different in the aCPu and NAc for any of the stimulation conditions. After a 40 min superfusion with (+)‐amphetamine (1 μm), t1/2 for 1p, 4p/10 Hz and 20p/20 Hz was significantly increased in both the aCPu and NAc, the increase in t1/2 being significantly greater in the aCPu than in the NAc. In conclusion, this study indicates that the dopamine displacement and uptake inhibitory actions of (+)‐amphetamine result in complex and differential effects on electrically evoked dopamine overflow in the aCPu and NAc. 1994 British Pharmacological Society