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Role of the substantia nigra in the expression of dopamine D1 receptor-mediated and D2 receptor-mediated behaviours.

Abstract：

:This study examines the proposal that striatonigral pathways support circling mediated by dopamine D1 receptors, but not D2 receptors, in unilaterally 6-hydroxydopamine-treated rats. In this model the D1/D2 agonist apomorphine, the D1 agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride and the D2 agonists N-n-propyl-N-phenylethyl-P-(3-hydroxyphenyl) ethylamine hydrochloride, trans-(-)-4aR,4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H-pyrazolo-(3, 4-g) quinolino monohydrochloride and lisuride evoked a characteristic spectrum of motor responses when administered systemically. In addition apomorphine, 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride and lisuride replicated their systemic effects following stereotaxic injection into the supersensitive caudate nucleus. Three months after injecting the pars reticulata of the dopamine-denervated nigra with kainic acid (1 microgram in 1 microliter), all motor responses to intracaudate dopamine agonists were reduced or abolished. Systemic responses were modified differentially, often as early as one day post-kainate. Contraversive circling and posturing were reduced, or even reversed (apomorphine only), grooming was attenuated (all drugs) and 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride-induced forepaw nibbling and dyskinesia were abolished. By contrast, sniffing, movements of the head and locomotion were either unaffected, or significantly potentiated, suggesting these components of behaviour arose from dopamine receptors outside the denervated striatum. These behavioural changes showed no signs of recovery three months after kainate, and were not produced by partial lesions of the reticulata (1 microgram kainate in 0.2 microliter). Contrary to earlier opinion our results indicate that the structural integrity of the substantia nigra pars reticulata is essential for the development of all forms of dopamine behaviour mediated by striatal D1 and D2 receptors, though not necessarily by dopamine receptors present at other locations.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Fletcher GH,Starr MS

doi

10.1016/0306-4522(87)90175-8

subject

Has Abstract

pub_date

1987-12-01 00:00:00

pages

1001-10

issue

3

eissn

0306-4522

issn

1873-7544

pii

0306-4522(87)90175-8

journal_volume

23

pub_type

杂志文章

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