Intrastriatal injection of GDNF attenuates the effects of 6-hydroxydopamine.
Our study was designed to determine whether intrastriatal administration of glial cell line-derived neurotrophic factor (GDNF) can attenuate the behavioral effects and injury to the mesostriatal dopaminergic system caused by 6-hydroxydopamine (6-OHDA). Four groups of rats received a series of four intrastriatal injections of vehicle or one of three doses of GDNF (0.1, 1 or 10 micrograms per injection) on days 1,3,5 and 8. On day 4 the animals received a single, intrastriatal injection of 25 micrograms 6-OHDA. Treatment with GDNF significantly reduced the development of amphetamine-induced rotation, and the dose of 1 microgram per injection appeared to be the most effective. The group treated with this dose had significantly greater preservation of tyrosine hydroxylase-immunoreactive (TH-IR) fibers adjacent to the injection site in the striatum and significantly greater preservation of Nissl-stained and TH-IR neurons in the substantia nigra pars compacta (SNpc).
Shults
C W
CW
Veterans Affairs Medical Center, San Diego, CA 92161, USA.
Kimber
T
T
Martin
D
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D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D005260:Female; D051100:Glial Cell Line-Derived Neurotrophic Factor; D007150:Immunohistochemistry; D007267:Injections; D017072:Neostriatum / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D016627:Oxidopamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects; D013565:Sympatholytics / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D015259:Dopamine Agents; D018491:Dopamine Agonists; C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D013565:Sympatholytics; D016627:Oxidopamine; D000661:Amphetamine; D001058:Apomorphine