Substance P and neurokinin A regulate by different mechanisms dopamine release from dendrites and nerve terminals of the nigrostriatal dopaminergic neurons

Numerous striatal neurons innervating the substantia nigra contain substance P and/or neurokinin A. In contrast to substance P or neurokinin A, little neurokinin B is found in the substantia nigra. This led us to compare the effects of nigral application of these tachykinins on the release of dopamine from dendrites and nerve terminals of nigrostriatal dopaminergic neurons. Experiments were made in halothane-anesthetized cats implanted with one push-pull cannula in the substantia nigra and another in the ipsilateral caudate nucleus [3H]Tyrosine was delivered continuously to each push-pull cannula and the release of newly synthesized [3H]dopamine measured in the superfusate. Unlike substance P or neurokinin A, neurokinin B (10(-8) M) applied for 30 min into the pars compacta of the substantia nigra was without effect on the release of [3H]dopamine from nerve terminals or dendrites. When either substance P (10(-8) M) or neurokinin A (10(-8) M) was applied into the pars compacta, the release of [3H]dopamine from nerve terminals was enhanced. While neurokinin A also stimulated the dendritic release of [3H]dopamine, this was reduced by substance P. At a lower concentration (10(-9) M), neurokinin A induced similar effects to those observed at 10(-8) M whereas substance P (10(-9) M) stimulated moderately [3H]dopamine release from nerve terminals but did not affect the dendritic release of the [3H]amine. When superfused into the pars reticulata, substance P (10(-8) M) still stimulated [3H]dopamine release from nerve terminals but not from dendrites while neurokinin A (10(-8) M) was without effect either in the caudate nucleus or the substantia nigra. Additional experiments were made to determine whether or not substance P (10(-8) M) or neurokinin A (10(-8) M) act directly on nigral dopaminergic neurons when applied into the pars compacta. The effects of substance P on [3H]dopamine release from nerve terminals and dendrites were prevented when 2-amino-6-trifluoromethoxy benzothiazole (10(-5) M), an antagonist of glutamatergic transmission, was applied continuously into the caudate nucleus. In contrast, the stimulatory effects of neurokinin A on [3H]dopamine release from nerve terminals and dendrites were insensitive to 2-amino-6-trifluoromethoxy benzothiazole (10(-5) M). These results suggest that neurokinin A, but not substance P, acts directly on dopaminergic cells. In the light of previous observations, we propose that the effects of substance P on dopaminergic transmission are mediated by a nigro-thalamo-cortico-striatal loop.(ABSTRACT TRUNCATED AT 400 WORDS)