EVIDENCE FOR ASPARTATE-IMMUNOREACTIVE NEURONS IN THE NEOSTRIATUM OF THE RAT - MODULATION BY THE MESENCEPHALIC DOPAMINE PATHWAY VIA D-1-SUBTYPE OF RECEPTOR

Aspartate-like immunoreactivity was visualized in the neostriatum of r ats using indirect immunofluorescence techniques and antibodies raised against aspartate conjugated to keyhole limper hemocyanine. In normal rats only a few aspartate-positive cell bodies with limited processes were observed. A moderate increase was seen after treatment with (+)m ethamphetamine and haloperidol. A dramatic increase in the number and fluorescence intensity was observed in the unilaterally 6-hydroxydopam ine lesioned rats after multiple injections of the D-1-dopamine recept or 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 antagon ist 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 ipsil ateral side outside the neostriatum, for example in the islet of Calle ja and in the piriform cortex. The aspartate-positive cells were negat ive for dopamine- and cyclic AMP-regulated phosphoprotein-32, a marker for neurons bearing dopamine D-1-receptor subtype. A proportion of th e aspartate-positive neurons (20%) contained neuropeptide tyrosine-lik e immunoreactivity. On adjacent sections there was a marked up-regulat ion of preprodynorphin-like immunoreactivity. The up-regulation of dyn orphin and aspartate was only observed when there was an almost comple te denervation of the neostriatum as visualized with antiserum to tyro sine hydroxylase, a marker for dopamine fibres. The present results ra ise the possibility that aspartate may act as a neurotransmitter relea sed from interneurons in the neostriatum. Copyright (C) 1996 IBRO.