Actions of cocaine on rat dopaminergic neurones in vitro

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Abstract
1 Intracellular recordings were made from neurones in vitro in the rat substantia nigra zona compacta and ventral tegmental area; the neurones had the characteristic properties of dopamine-containing cells, and fired action potentials spontaneously. 2 Cocaine (1–10μm) inhibited spontaneous firing, hyperpolarized the membrane and (in neurones voltage-clamped at −60 mV) caused an outward membrane current; the minimally effective concentration was 1 μm. These effects were blocked by sulpiride (30 nm–1 μm). 3 Dopamine (3–100 μm) also inhibited firing, hyperpolarized and caused an outward current. These effects of dopamine were potentiated about five fold by cocaine (10 μm). 4 It is concluded that cocaine (1–10 μm) inhibits the firing and hyperpolarizes substantia nigra zona compacta neurones in vitro by blocking the uptake of dopamine which the cells continuously release.