ELECTROPHYSIOLOGICAL EFFECTS OF AMINEPTINE ON NEURONS 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-mu-M) 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-mu-M) but it was abolished in 0 mM Ca2+ (plus 13 mM MgCl2) solutions. 4 Amineptine (300 nM-30-mu-M) and cocaine (10-30-mu-M) increased the amplitude and duration of responses to exogenously applied dopamine. The effects of dopamine were potentiated about 5 fold by 10-mu-M amineptine; this potentiation persisted in calcium-free solutions. 5 Cocaine (10-mu-M) had no additional effect on the dopamine-induced responses in the presence of amineptine (30-mu-M). Amineptine (10-mu-M) produced no detectable effects in the presence of cocaine (30-mu-M). 6 It is concluded that amineptine acts as a dopamine uptake blocker in slices of rat substantia nigra.