EVIDENCE FOR ASPARTATE-IMMUNOREACTIVE NEURONS IN THE NEOSTRIATUM OF THE RAT: MODULATION BY THE MESENCEPHALIC DOPAMINE PATHWAY VIA D1-SUBTYPE OF RECEPTOR

Abstract Aspartate-like immunoreactivity was visualized in the neostriatum of rats using indirect immunofluorescence techniques and antibodies raised against aspartate conjugated to keyhole limpet hemocyanine. In normal rats only a few aspartate-positive cell bodies with limited processes were observed. A moderate increase was seen after treatment with (+)methamphetamine and haloperidol. A dramatic increase in the number and fluorescence intensity was observed in the unilaterally 6-hydroxy-dopamine lesioned rats after multiple injections of the D 1 -dopamine receptor agonist SKF 38393. In these rats strongly fluorescent processes as well as extensive terminal varicose fibre networks were observed. This increase could partly be blocked by the D 1 -dopamine receptor antagonist SCH 23390. Using a modified technique the aspartate-positive cell bodies and processes were observed even when the antiserum was diluted 1:80.000. Positive cell bodies and fibres were also seen on the ipsilateral side outside the neostriatum, for example in the islet of Calleja and in the piriform cortex. The aspartate-positive cells were negative for dopamine- and cyclic AMP-regulated phosphoprotein-32, a marker for neurons bearing dopamine D 1 -receptor subtype. A proportion of the aspartate-positive neurons (20%) contained neuropeptide tyrosine-like immunoreactivity. On adjacent sections there was a marked up-regulation of preprodynorphin-like immunoreactivity. The up-regulation of dynorphin and aspartate was only observed when there was an almost complete denervation of the neostriatum as visualized with antiserum to tyrosine hydroxylase, a marker for dopamine fibres. The present results raise the possibility that aspartate may act as a neurotransmitter released from interneurons in the neostriatum. Copyright © 1996 IBRO. Published by Elsevier Science Ltd.