Simultaneous recording of the release of nigral and striatal dopamine in the awake rat.

The extracellular concentration of dopamine (DA) and 3,4-hydroxyphenylacetic acid (DOPAC) were estimated in the substantia nigra and striatum by microdialysis. The dialysate content of DA increased at least 10-fold when nomifensine (5 mumol/l) was infused into the nigra via the dialysis membrane. To improve the analytical chemical detection of DA, nomifensine was infused continually during all the dialysis experiments that were carried out in the substantia nigra. Dendritic as well as terminal release of DA were inhibited for several hours when the nerve impulse flow in dopaminergic neurons was blocked by systemic administration of gamma-butyrolacton (750 mg/kg, i.p.). Perfusion of tetrodotoxin through the nigra (1 mumol/l) produced a complete disappearance of nigral DA release and a somewhat variable decrease in the release of striatal dopamine. When tetrodotoxin was infused into the nigra, the DOPAC output from the nigra was unchanged, but striatal DOPAC increased to about 300% of controls. These results show that the dendritic release of DA fulfills classical release criteria: it possesses an effective uptake-mechanism, it is dependent on the opening of fast-sodium channels and it is related to drug-induced changes in impulse-flow activity.