In vivo microdialysis studies of somatodendritic dopamine release in the rat substantia nigra: Effects of unilateral 6-OHDA lesions and GDNF

Alexander F. Hoffman, Craig G. Van Horne, Servet Eken, Barry J. Hoffer, Greg A. Gerhardt

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51 Scopus citations

Abstract

Dopamine (DA) release and metabolism within the substantia nigra (SN) were studied in normal rats, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions, and 6-OHDA-lesioned rats treated with glial cell line-derived neurotrophic factor (GDNF). Animals with >99% DA depletions, as determined by apomorphine-induced circling behavior, also showed significant deficits in several measures of spontaneous motor activity. In vivo microdialysis recordings in the SN were carried out in normal and unilaterally 6-OHDA- lesioned rats. Basal levels of DA were detectable only in the dialysates of normal animals, and basal levels of the primary DA metabolites 3,4- dihydroxyphenylacetic acid and homovanillic acid were found to be significantly reduced in the SN of 6-OHDA-lesioned animals. In the presence of d-amphetamine, either alone or in combination with potassium, significant reductions in DA release were observed in the SN of 6-OHDA-lesioned animals compared to normal animals. Potassium-evoked DA release alone was not significantly different between the groups. A single intranigral administration of GDNF into 6-OHDA-lesioned animals elicited a significant reduction in apomorphine-induced rotation behavior and a significant increase in spontaneous motor activities. These behavioral changes were apparent at 1 week and persisted through 4 weeks following treatment. In vivo microdialysis showed that, although DA metabolism was altered 1 week following GDNF treatment, DA release was not significantly affected until 4 weeks following treatment.

Original languageEnglish
Pages (from-to)130-141
Number of pages12
JournalExperimental Neurology
Volume147
Issue number1
DOIs
StatePublished - Sep 1997

Bibliographical note

Funding Information:
The authors thank Ron Maloney for assistance in the preparation of the microdialysis probes, Karen Giardina for her assistance with histology, and Pete Huettl and Scot Brock for their invaluable assistance with the HPLC-EC. This research was supported in part by grants from USPHS AG06434, NS09199, NSF BNS9110308, and GM07635.

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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