Protection by GDNF and other trophic factors against the dopamine-depleting effects of neurotoxic doses of methamphetamine.
Repeated methamphetamine (METH) administration to animals can result in long-lasting decreases in striatal dopamine (DA) content. It has previously been shown that glial cell line-derived neurotrophic factor (GDNF) can reduce the DA-depleting effects of neurotoxic doses of METH. However, there are several other trophic factors that are protective against dopaminergic toxins. Thus, the present experiments further investigated the protective effect of GDNF as well as the protective effects of several other trophic factors. Male Fischer-344 rats were given an intracerebral injection of trophic factor (2-10 microg) 1 day before METH (5 mg/kg, s.c., 4 injections at 2-h intervals). Seven days later DA levels in the striatum were measured using high-performance liquid chromatography (HPLC). Initial experiments indicated that only intrastriatal GDNF, and not intranigral GDNF, was protective. Thereafter, all other trophic factors were administered into the striatum. Members of the GDNF family (GDNF, neurturin, and artemin) all provided significant protection against the DA-depleting effects of METH, with GDNF providing the greatest protection. Brain-derived neurotrophic factor, neurotrophin-3, acidic fibroblast growth factor, basic fibroblast growth factor, ciliary neurotrophic factor, transforming growth factor-alpha (TGF-alpha), heregulin beta1 (HRG-beta1), and amphiregulin (AR) provided no significant protection at the doses examined. These results suggest that the GDNF family of trophic factors can provide significant protection against the DA-depleting effects of neurotoxic doses of METH.
Cass
Wayne A
WA
Department of Anatomy and Neurobiology, MN-225 Chandler Medical Center, University of Kentucky, Lexington, KY 40536-0298, USA. wacass1@uky.edu
Peters
Laura E
LE
Harned
Michael E
ME
Seroogy
Kim B
KB
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000633:toxicity*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000008:administration & dosage*; D008297:Male; D008694:Methamphetamine / Q000633:toxicity*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D015259:Dopamine Agents; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D008694:Methamphetamine; D004298:Dopamine