A quantitative comparison on the effects of benztropine, cocaine and nomifensine on electrically evoked dopamine overflow and rate of re-uptake in the caudate putamen and nucleus accumbens in the rat brain slice.
Fast cyclic voltammetry has been used to study the relative importance of neuronal dopamine (DA) uptake and D2 autoreceptor stimulation on the control of the extracellular concentration of electrically evoked DA in rat brain slices containing aCPu and NAc. The degree of potentiation of DA overflow by benztropine, cocaine and nomifensine was always greater in the aCPu than in the NAc. Although EC50 values for the uptake blockers in the NAc were lower than in the aCPu, they were only significantly lower for 1 p with benztropine. One microM (-)-sulpiride, significantly potentiated DA overflow evoked by 20 p/20 Hz in both regions. In the presence of either 1 microM cocaine or 1 microM nomifensine, sulpiride further potentiated DA overflow in the NAc but not in the aCPu. The results indicate that in brain slices containing the aCPu, neuronal uptake is the main mechanism of controlling extracellular concentrations of DA due to electrical stimulation. Whilst in the NAc both uptake and D2 autoreceptor activation are important control mechanisms. The rate of removal of DA from the extracellular medium was not significantly different in the two regions but was decreased in the presence of (-)-sulpiride. This indicates that D2 receptors have a modulating effect on the DA neuronal uptake mechanism.
Wieczorek
W J
WJ
Department of Pharmacology, Medical Sciences, Queen Mary and Westfield College, London, UK.
Kruk
Z L
ZL
D000818:Animals; D001590:Benztropine / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009627:Nomifensine / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013469:Sulpiride / Q000494:pharmacology
D009627:Nomifensine; D001590:Benztropine; D013469:Sulpiride; D003042:Cocaine; D004298:Dopamine