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Brain Res. 1993 May 28;612(1-2):306-12.

Effect of neurotensin and immunneutralization with anti-neurotensin-serum on dopaminergic-cholinergic interaction in the striatum.

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Institute of Experimental Medicine, Hungarian Academy of Sciences, Budapest.


The effect of neurotensin (NT) on the release of acetylcholine (ACh) and dopamine (DA) from striatal slices of the rat brain was studied. Neurotensin, 1-150 nM, was able to release ACh from cholinergic interneurons of the striatum. Like the response to electrical stimulation, the ACh-releasing effect of NT was completely inhibited by tetrodotoxin indicating that neuronal firing is involved in its effect. Immunneutralization reduced the stimulation-evoked release of ACh, an effect that was much marked when the inhibitory dopaminergic input was suspended by sulpiride-selective antagonists of D2 receptors. Sulpiride, 0.1 mM, induced a 2-fold increase in the NT- and electrically-induced release of ACh. A quantitatively similar increase was also observed after degeneration of the nigrostriatal DA pathway with 6-hydroxydopamine (6-OHDA) (2 x 250 micrograms/animal, i.c.v.). However, the D2 receptor agonist quinpirole, 0.01 mM, significantly reduced the NT-induced release of ACh by 77%. Neurotensin enhanced the stimulation-evoked release of [3H]DA. These findings indicate that, using field stimulation when dopaminergic, cholinergic and NT-containing neurons are stimulated in concert, NT is capable of releasing both ACh and DA in the striatum, but its effect on ACh release is masked unless the D2 receptor-mediated tonic inhibitory effect of DA released from the nigro-striatal pathway is attenuated. Thus, in Parkinson's disease where the dopaminergic input is impaired, NT may be involved in producing cholinergic dominance.

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