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Intensification of cataleptic response in 6‐hydroxydopamine‐induced neurodegeneration of substantia nigra is not dependent on the degree of dopamine depletion
Author(s) -
Srinivasan J.,
Schmidt Werner J.
Publication year - 2003
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10297
Subject(s) - catalepsy , substantia nigra , dopamine , hydroxydopamine , endocrinology , context (archaeology) , medicine , medial forebrain bundle , homovanillic acid , basal ganglia , chemistry , neuroscience , striatum , psychology , dopaminergic , biology , central nervous system , paleontology , receptor , serotonin , haloperidol
An intensification of catalepsy has been observed upon repeated testing in rats with permanent neurodegeneration of substantia nigra. Here, the question is addressed whether the rate of development of intensification of catalepsy upon repeated testing in the same context is dependent on dopamine level in the basal ganglia. Rats were lesioned with 2 μg or 6 μg of 6‐hydroxydopamine in the median forebrain bundle to produce dopamine depletion in substantia nigra in two different proportions. Both groups were exposed to catalepsy tests for 7 successive days in the same context, and the context was changed on day 8. On day 9 the catalepsy test was repeated with the old context. After the completion of the behavioral experiments, various regions of basal ganglia were analyzed for dopamine and its metabolites 3,4‐dihydroxyphenylacetic acid, 3‐methyl tyronine, and homovanillic acid. Lesions with 6 μg of 6‐hydroxydopamine produced strong dopamine depletion (78%) and akinetic response in the catalepsy test on day 1. Repeated exposure of this group to the catalepsy tests in the same context produced intensification of cataleptic response. Changing the context on day 8 reduced catalepsy. Performing the experiments again with the old context on day 9 produced an intensified response. Lesions with 2 μg of 6‐hydroxydopamine produced partial dopamine depletion (46%) without any motor disturbances. However, repeated exposure and context changes produced a similar pattern of catalepsy as in the 6 μg lesioned animals. These results indicate that the rate of building up of intensification of catalepsy is not dependent on the degree of dopamine depletion. It signifies the importance of context in the expression and augmentation of parkinsonian symptoms during the course of the disease to subjects with subthreshold dopaminergic neurodegeneration that could not produce motor disturbances alone. Prevention of context‐dependent intensification of catalepsy could be beneficial in the treatment of Parkinson's disease. Synapse 51:213–218, 2004. © 2003 Wiley‐Liss, Inc.