Dopamine uptake inhibition potentiates the effects of L-DOPA on rat substantia nigra zona compacta neurons.

Intracellular electrophysiological recordings (current and voltage-clamp mode) were used to assess whether the actions of L-DOPA on rat substantia nigra zona compacta neurons maintained in vitro are potentiated by drugs that block the dopamine uptake system (cocaine and nomifensine). Bath application of L-DOPA (100 microM) hyperpolarized the dopaminergic cells and inhibited the spontaneous occurring action potential discharge. Under voltage-clamp experiments, L-DOPA produced an outward current that was related to the hyperpolarization of the membrane. In the presence of 10 microM cocaine and 10 microM nomifensine, the cellular responses to L-DOPA application were augmented and prolonged. In contrast to this, amphetamine (a dopamine releasing drug), did not augment the membrane response to L-DOPA. Cocaine (10 microM), nomifensine (10 microM) and amphetamine (3 microM), slightly hyperpolarized the membrane potential and inhibited the firing activity of the cells. It is concluded that the dopamine uptake system have an important role in regulating the cellular responses (membrane hyperpolarization or outward current) to L-DOPA application in the substantia nigra zona compacta.