Reversal of akinesia in experimental parkinsonism by GABA antagonist microinjections in the pedunculopontine nucleus

Recent studies, mainly in animals, have shown that the pedunculopontine nucleus (PPN) in the upper brainstem has extensive connections with several motor centres in the CNS. This structure has also been implicated in the akinesia seen in patients with Parkinson’s disease. Here we demonstrate that mi...

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Veröffentlicht in:	Brain (London, England : 1878) England : 1878), 2002-11, Vol.125 (11), p.2418-2430
Hauptverfasser:	Nandi, Dipankar, Aziz, Tipu Z., Giladi, Nir, Winter, Jonathan, Stein, John F.
Format:	Artikel
Sprache:	eng
Schlagworte:	1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine 6‐tetrahydropyridine akinesia Animals bicuculline Bicuculline - pharmacology Biological and medical sciences Cholinergic Fibers - drug effects Cholinergic Fibers - metabolism Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Female GABA Antagonists - pharmacology GABA-A Receptor Antagonists GABA = γ‐aminobutyric acid gamma-Aminobutyric Acid - metabolism gamma‐aminobutyric acid GIC = Global Impression of Change GPi = medial globus pallidus Levodopa - pharmacology Macaca mulatta Male Medical sciences Motor Activity - drug effects Motor Activity - physiology MPTP = 1‐methyl‐4‐phenyl‐1 Neural Inhibition - drug effects Neural Inhibition - physiology Neural Pathways - drug effects Neural Pathways - physiopathology Neurology Parkinsonian Disorders - drug therapy Parkinsonian Disorders - physiopathology pedunculopontine nucleus Pons - drug effects Pons - physiopathology PPMRS = Primate Parkinsonism Motor Rating Scale PPN = pedunculopontine nucleus Primates Receptors, GABA-A - metabolism Recovery of Function - drug effects Recovery of Function - physiology STN = subthalamic nucleus Tegmentum Mesencephali - drug effects Tegmentum Mesencephali - physiopathology Treatment Outcome VPPMRS = Video PPMRS
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Zusammenfassung:	Recent studies, mainly in animals, have shown that the pedunculopontine nucleus (PPN) in the upper brainstem has extensive connections with several motor centres in the CNS. This structure has also been implicated in the akinesia seen in patients with Parkinson’s disease. Here we demonstrate that microinjection of γ‐aminobutyric acid (GABA) receptor A antagonist substance, bicuculline, into the PPN of non‐human primates (n = 2) rendered parkinsonian with 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) results in significant improvement of akinesia. The effect of bicuculline microinjection in the PPN matches that of oral administration of l‐dopa. This finding opens up new possibilities in the management of akinesia, the most intractable symptom of advanced Parkinson’s disease.
ISSN:	0006-8950 1460-2156 1460-2156
DOI:	10.1093/brain/awf259