Abstract
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 gamma-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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
-
Animals
-
Bicuculline / pharmacology*
-
Cholinergic Fibers / drug effects
-
Cholinergic Fibers / metabolism
-
Female
-
GABA Antagonists / pharmacology*
-
GABA-A Receptor Antagonists
-
Levodopa / pharmacology
-
Macaca mulatta
-
Male
-
Motor Activity / drug effects
-
Motor Activity / physiology
-
Neural Inhibition / drug effects*
-
Neural Inhibition / physiology
-
Neural Pathways / drug effects
-
Neural Pathways / physiopathology
-
Parkinsonian Disorders / drug therapy*
-
Parkinsonian Disorders / physiopathology
-
Pons / drug effects*
-
Pons / physiopathology
-
Receptors, GABA-A / metabolism
-
Recovery of Function / drug effects
-
Recovery of Function / physiology
-
Tegmentum Mesencephali / drug effects*
-
Tegmentum Mesencephali / physiopathology
-
Treatment Outcome
-
gamma-Aminobutyric Acid / metabolism*
Substances
-
GABA Antagonists
-
GABA-A Receptor Antagonists
-
Receptors, GABA-A
-
Levodopa
-
gamma-Aminobutyric Acid
-
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
-
Bicuculline