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D1 dopamine receptor-mediated substance P depletion in the striatonigral neurons of rats subjected to neonatal dopaminergic denervation: implications for self-injurious behavior.

Abstract：

:The present study examined the influences of dopamine (DA) receptor stimulation on enkephalin (Met5-enkephalin; ME) and tachykinin (substance P; SP) systems of basal ganglia of Sprague-Dawley rats, lesioned as neonates with 6-hydroxydopamine (6-OHDA). It has been proposed that the neonatal 6-OHDA-lesioned rat could serve as a model for the DA deficiency and self-injurious behavior (SIB) observed in the childhood neurological disorder. Lesch-Nyhan syndrome. In agreement with earlier work, the present study found that the neonatal 6-OHDA treatment at 3 days of age, reduced DA and caused an increase in ME and a decrease in SP content in the striatum and substantia nigra, when tested as adults. Administration of the DA precursor, L-dihydroxyphenylalanine (L-DOPA), to lesioned animals, induced SIB; increased DA and DOPAC levels; produced a greater decrease (-64%) in SP levels in the striatum and substantia nigra than was observed with lesion alone (-28%). The L-DOPA-induced decrease in SP levels and the SIB observed in the lesioned animals were blocked by pretreatment with the D1 receptor antagonist, SCH-23390. Moreover, administration of the D1 receptor agonist, SKF-38393, but not the D2 agonist, LY-171555, to lesioned animals mimicked the L-DOPA responses in all respects, except that the agonists did not alter DA or DOPAC levels. None of the DA agonists or antagonists treatments affected lesion-induced increase in ME levels in the striatum. These results indicate for the first time, that SIB precipitated by DA agonists in neonatal dopaminergic denervated animals, is associated with a marked and selective decrease in SP in the striatonigral SP neurons. This process has two components: (a) a retarded development of the SP system due to neonatal dopaminergic denervation: and (b) a depletion of the remaining SP, presumably by enhanced release due to D1 DA receptor-mediated activation of striatonigral SP neurons.

journal_name

Brain Res

journal_title

Brain research

authors

Sivam SP

doi

10.1016/0006-8993(89)90305-3

subject

Has Abstract

pub_date

1989-10-23 00:00:00

pages

119-30

issue

1-2

eissn

0006-8993

issn

1872-6240

pii

0006-8993(89)90305-3

journal_volume

500

pub_type

杂志文章

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D1 dopamine receptor-mediated substance P depletion in the striatonigral neurons of rats subjected to neonatal dopaminergic denervation: implications for self-injurious behavior.