IN-VIVO MICRODIALYSIS STUDIES OF 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 cell line- derived neurotrophic factor (GDNF). Animals with >99% DA depletions, a s determined by apomorphine-induced circling behavior, also showed sig nificant deficits in several measures of spontaneous motor activity. I n vivo microdialysis recordings in the SN were carried out in normal a nd unilaterally 6-OHDA-lesioned rats. Basal levels of DA were detectab le only in the dialysates of normal animals, and basal levels of the p rimary DA metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid were found to be significantly reduced in the SN of 6-OHDA-lesion ed animals. In the presence of d-amphetamine, either alone or in combi nation with potassium, significant reductions in DA release were obser ved in the SN of 6-OHDA-lesioned animals compared to normal animals. P otassium-evoked DA release alone was not significantly different betwe en the groups. A single intranigral administration of GDNF into 6-OHDA -lesioned animals elicited a significant reduction in apomorphine-indu ced rotation behavior and a significant increase in spontaneous motor activities. These behavioral changes were apparent at 1 week and persi sted through 4 weeks following treatment. In vivo microdialysis showed that, although DA metabolism was altered 1 week following GDNF treatm ent, DA release was not significantly affected until 4 weeks following treatment. (C) 1997 Academic Press.