Article date: 1990/5/1
PubMed ID: 2139853
Journal name: Experimental neurology (ISSN: 0014-4886)
Unilateral caudate-putamen (CP) lesions induced by the glutamate receptor agonist ibotenic acid in baboons produced a neuropathological and behavioral model of Huntington's disease (HD) in the nonhuman primate. Neuropathological evaluation of the lesioned caudate-putamen revealed a neurodegenerative pattern resembling HD. The ibotenic acid-infused CP areas showed a neuronal loss in Nissl-stained sections and a marked astrocytic gliosis by immunohistochemical staining for glial-fibrillary-acidic protein. Acetylcholinesterase fiber staining was severely reduced in the lesioned CP, while afferent dopaminergic fibers, as shown by tyrosine hydroxylase staining, were relatively spared. There was a moderate reduction of met-enkephalin staining in the globus pallidus-pars lateralis ipsilateral to the ibotenic acid lesion, indicating a partial denervation of this structure following the lesion. In the behavioral studies a dyskinetic syndrome with features in common with HD was provoked in the lesioned animals following dopamine receptor agonist administration (1-2 mg/kg apomorphine). The symptoms included hyperkinesia, chorea, dystonia, postural asymmetries, head, and orofacial dyskinesia. The apomorphine test was highly reproducible and individual animals responded with a similar set and incidence of dyskinesia in successive tests. Since the behavioral observations following excitotoxic caudate-putamen damage parallel symptoms in HD patients given dopamine stimulatory drugs, a hypothesis is presented for the observed abnormal movements suggesting that the CP lesions reduce movement thresholds while the activation of dopaminoceptive regions induces dyskinesias.
Author List: Hantraye P, Riche D, Maziere M, Isacson O
Publication Types: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Ibotenic Acid; Apomorphine;
Mesh terms: Animals; Apomorphine/pharmacology; Behavior, Animal/drug effects; Brain Diseases/chemically induced; Caudate Nucleus/pathology; Disease Models, Animal; Dystonia/chemically induced; Female; Huntington Disease/pathology; Ibotenic Acid; Male; Motor Activity/drug effects; Movement; Papio; Putamen/pathology;