Increased striatal neuropeptide Y immunoreactivity and its modulation by deprenyl, clonidine and L-dopa in MPTP-treated mice.
The aim of this study was to evaluate the effect of MPTP (2 x 45 mg/kg s.c., 20 h apart) on striatal neuropeptide Y-like immunoreactivity (NPY-LI) in C57BL/6 mice. NPY-LI markedly increased 2 weeks after MPTP but it remained unchanged after 24 h, 1 or 6 weeks. The increase in NPY-LI was accompanied by depletion of dopamine (-80%), DOPAC (-70%), 3-MT (-44%) and HVA (-52%). L-Deprenyl completely prevented the MPTP-induced NPY-LI increase, neurodegeneration of the striatal dopamine system and motor dysfunction. Clonidine attenuated the neurotoxin effect on NPY-LI and dopaminergic neurons. L-dopa/carbidopa protected NPY neurons against MPTP but slightly enhanced MPTP-induced decrease in the levels of dopamine and its metabolites. The relationship between changes in NPY-LI and dopamine and serotonin metabolism determined by HPLC was discussed. The results further extend the range of MPTP-elicited modifications in striatum and demonstrate that drugs with antiparkinsonian activity can protect NPY neurons against MPTP toxicity.
Obuchowicz
E
E
Department of Clinical Pharmacology, Silesian Medical University, Katowice, Poland. eobuchowicz@slam.katowice.pl
Antkiewicz-Michaluk
L
L
Romańska
I
I
Herman
Z S
ZS
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D007150:Immunohistochemistry; D007980:Levodopa / Q000494:pharmacology; D020267:MPTP Poisoning / Q000188:drug therapy*; D008297:Male; D051379:Mice; D009478:Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D009478:Neuropeptide Y; D018696:Neuroprotective Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D012701:Serotonin; D007980:Levodopa; D003000:Clonidine; D004298:Dopamine; D006719:Homovanillic Acid