Differential action of (+)-amphetamine on electrically evoked dopamine overflow in rat brain slices containing corpus striatum and nucleus accumbens.
1. 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. 2. (+)-Amphetamine (1 microM) 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 microM and in the NAc was 0.270 +/- 0.04 microM. Pretreatment with (-)-sulpiride (1 microM) did not affect this action of (+)-amphetamine. 3. (+)-Amphetamine (1 microM) exhibited a complex and time-dependent effect on electrically stimulated dopamine overflow, evoked by 1p, 4p/10 Hz and 20p/20 Hz. 4. In the aCPu, (+)-amphetamine (1 microM) resulted in attenuation of dopamine overflow due to 1p and 4p/10 Hz but potentiation of dopamine overflow to 20p/20 Hz. (-)-Sulpiride (1 microM) prior to (+)-amphetamine (1 microM) 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. 5. (+)-Amphetamine (1 microM) potentiated dopamine overflow in the NAc to all three stimuli. (-)-Sulpiride (1 microM) prior to (+)-amphetamine (1 microM), resulted initially, in a further potentiation of overflow, followed by a time-dependent attenuation of dopamine overflow to all three stimuli. 6. 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 MicroM), t1/2 for ip, 4p/10 Hz and 20p/20 Hz was significantly increased in both the aCPuand NAc, the increase in t1/2 being significantly greater in the aCPu than in the NAc.7. 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.
Department of Pharmacology, Queen Mary & Westfield College, London.
W J
WJ
Wieczorek
Z L
ZL
Kruk
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology; D013469:Sulpiride / Q000494:pharmacology
D017448:Receptors, Dopamine D2; D013469:Sulpiride; D000661:Amphetamine; D004298:Dopamine