Dopamine Cell Degeneration Induced by Intraventricular Administration of 6-Hydroxydopamine in the Rat: Similarities with Cell Loss in Parkinson's Disease

• Published in: Experimental neurology Vol. 169; no. 1; pp. 163 - 181
• Main Authors: Rodrı́guez, Manuel, Barroso-Chinea, Pedro, Abdala, Patricio, Obeso, José, González-Hernández, Tomás
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.05.2001; Elsevier
• Subjects: 6-hydroxydopamine; animal model; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Calbindin 2; Calbindins; Cell Count; Cell Size; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; dopamine; Dopamine - metabolism; Dose-Response Relationship, Drug; Immunohistochemistry; Injections, Intraventricular; Male; Medical sciences; Mesencephalon - drug effects; Mesencephalon - pathology; Motor Activity - drug effects; Neurology; Neurons - metabolism; Neurons - pathology; Oxidopamine - administration & dosage; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson Disease, Secondary - chemically induced; Parkinson's disease; Rats; Rats, Sprague-Dawley; S100 Calcium Binding Protein G - metabolism; Third Ventricle - drug effects; Tyrosine 3-Monooxygenase - metabolism; vulnerability; 6-hydroxydopamine; Parkinson's disease; vulnerability; animal model; dopamine; Tyrosine; Animal model; Nervous system diseases; Calbindin; Dopamine; Calretinin; Rat; Motor system disorder; Rodentia; Parkinson disease; Midbrain; Cerebral ventricle; Cerebral disorder; Vertebrata; Mammalia; Animal; Central nervous system disease; Dopaminergic neuron; Degenerative disease; Degeneration; Extrapyramidal syndrome
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2000.7624

In an attempt to find a convenient rat model to study cell vulnerability in Parkinson's disease, we have investigated the cell-loss profile in different midbrain dopaminergic nuclei and subnuclei of rats injected with 6-hydroxydopamine (6-OHDA) in the third ventricle. Following administration of different doses (5–1000 μg) of 6-OHDA, motor behavior was evaluated and tyrosine hydroxylase-immunostained neurons were counted in the A8 group and different subdivisions of A9 and A10 groups. Animals developed hypokinesia, repetitive chewing movements, and catalepsia. Signs of cell degeneration were evident from the first day after injection, reaching the definitive pattern at the end of the first week. There was a similar degeneration in both brain sides, the A9 group showing the highest degree of cell-loss, followed by A8 and A10 groups. In the A9 group, the degeneration mostly affected those subgroups located in its ventral, lateral, and posterior regions. In the A10 group the degeneration mainly affected the parabrachial pigmented nucleus, the paranigral nucleus and the ventral tegmental area. This topographic pattern of degeneration is very similar to that previously described in Parkinson's disease, suggesting that this model may be a useful tool in the study of the cell vulnerability mechanisms in this neurodegenerative disorder. In addition, our results also showed that small dopaminergic neurons are more resistant to degeneration than the large ones. In some DA subgroups, the cells that contained calbindin but not calretinin were less vulnerable to the neurotoxic effect of 6-OHDA.