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Neurochemical mechanisms of actions of atypical neuroleptics carbidine (a derivative of gamma-carboline) and sulpiride on dopamine (DA) biosynthesis in synaptosomes of the nucleus accumbens septi of the rat brain were studied. Carbidine caused a dose-dependent decrease of the animals' locomotor hyperactivity induced by apomorphine (1 mg/kg). Both carbidine and sulpiride administered in a dose of 5 mg/kg increased the activity of tyrosine hydroxylase in synaptosomes of the nucleus accumbens septi. In vitro carbidine decreased and sulpiride exerted no effect on the activity of tyrosine hydroxylase of the nucleus accumbens septi synaptosomes. Carbidine as well as sulpiride in vitro failed to modify the release of 3H-DA from superfused synaptosomes. At the same time, both in vivo and in vitro, the two neuroleptics reduced the inhibitory effect of DA on the 3H-DA release from synaptosomes of the nucleus accumbens septi and on the activity of tyrosine hydroxylase.
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