Intrapallidal dopamine restores motor deficits induced by 6-hydroxydopamine in the rat.
To explore whether dopamine deficits in the globus pallidus have a role in generating the motor symptoms of Parkinson's disease, we examined the effects of selective intrapallidal administration of dopamine or its antagonists in rats unilaterally lesioned with 6-hydroxydopamine into the medial forebrain bundle. Either the turning behavior induced by apomorphine or the deficit in the performance of a skilled forelimb-reaching task was used as assay for drug action. Microinjection of either the D2 receptor antagonist, sulpiride, or the D1 receptor antagonist, SCH-23390, into the dopamine-denervated pallidum significantly reduced apomorphine induced turning. In animals trained to perform a skilled forelimb-reaching task, 6-OHDA lesions caused a marked motor deficit in the contralateral forelimb. Intrapallidal dopamine applied either intermittently or continuously, restored up to 50% of the motor performance. Continuous application promoted a motor recovery that outlasted dopamine administration. These results show that lack of dopamine in the GP plays an important role in generating the motor symptoms caused by lesion of dopaminergic pathways. Moreover, motor recovery was produced by selectively injecting dopamine into the globus pallidus.
Galvan
A
A
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, México.
Floran
B
B
Erlij
D
D
Aceves
J
J
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D005917:Globus Pallidus / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009410:Nerve Degeneration / Q000139:chemically induced / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D020127:Recovery of Function / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D013565:Sympatholytics; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D001552:Benzazepines; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013565:Sympatholytics; D005680:gamma-Aminobutyric Acid; D013469:Sulpiride; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine