In vivo microdialysis studies on somatodendritic dopamine release in the rat substantia nigra: effects of unilateral 6-OHDA lesions and GDNF.
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 cells 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 DNA were detectable only in the dialysates of normal animals, and basal levels of t he 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.
Hoffman
A F
AF
Department of Pharmacology, University of Colorado Health, Sciences Center, Denver 80262, USA.
van Horne
C G
CG
Eken
S
S
Hoffer
B J
BJ
Gerhardt
G A
GA
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003712:Dendrites / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016627:Oxidopamine / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values; D013239:Stereotyped Behavior / Q000187:drug effects; D013268:Stimulation, Chemical; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
D018491:Dopamine Agonists; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine