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Electrophysiological effects of amineptine on neurones of the rat substantia nigra pars compacta: evidence for an inhibition of the dopamine uptake system
Author(s) -
Mercuri N.B.,
Stratta F.,
Calabresi P.,
Bernardi G.
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb12491.x
Subject(s) - substantia nigra , dopamine , pars compacta , chemistry , sulpiride , pharmacology , electrophysiology , membrane potential , endocrinology , medicine , biology , dopaminergic , biochemistry
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 μ 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 μ m ) but it was abolished in 0 m m Ca 2+ (plus 13 m m MgCl 2 ) solutions. 4 Amineptine (300 n m ‐30 μ m ) and cocaine (10–30 μ m ) increased the amplitude and duration of responses to exogenously applied dopamine. The effects of dopamine were potentiated about 5 fold by 10 μ m amineptine; this potentiation persisted in calcium‐free solutions. 5 Cocaine (10 μ m ) had no additional effect on the dopamine‐induced responses in the presence of amineptine (30 μ m ). Amineptine (10 μ m ) produced no detectable effects in the presence of cocaine (30 μ m ). 6 It is concluded that amineptine acts as a dopamine uptake blocker in slices of rat substantia nigra.