Electrophysiological effects of amineptine on neurones of the rat substantia nigra pars compacta: evidence for an inhibition of the dopamine uptake system.

1. Intracellular recordings were made from substantia nigra pars compacta neurones of the rat maintained in vitro in order to study the effects of the tricyclic antidepressant drug, amineptine. 2. Amineptine hydrochloride (1-30 microM) decreased spontaneous firing and slightly hyperpolarized the membrane potential. In neurones voltage-clamped at -50 or -60 mV, amineptine produced an outward membrane current. These actions were concentration-dependent and were completely antagonized by (-)-sulpiride. 3. The amineptine-induced hyperpolarization was resistant to tetrodotoxin (1 microM) but it was abolished in 0 mM Ca2+ (plus 13 mM MgCl2) solutions. 4. Amineptine (300 nM-30 microM) and cocaine (10-30 microM) increased the amplitude and duration of responses to exogenously applied dopamine. The effects of dopamine were potentiated about 5 fold by 10 microM amineptine; this potentiation persisted in calcium-free solutions. 5. Cocaine (10 microM) had no additional effect on the dopamine-induced responses in the presence of amineptine (30 microM). Amineptine (10 microM) produced no detectable effects in the presence of cocaine (30 microM). 6. It is concluded that amineptine acts as a dopamine uptake blocker in slices of rat substantia nigra.