Neurobehavioral protection by single dose l-deprenyl against MPTP-induced parkinsonism in common marmosets.
OBJECTIVE
Establishment of preclinical method evaluating behavioral protective actions of drugs for Parkinson's disease was attempted using l-deprenyl (DEP) as a reference drug in 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated common marmosets.


METHODS
Fifteen marmosets received MPTP at 2 mg/kg, subcutaneously (s.c.) per day for three consecutive days. To these marmosets, intragastric (i.g.) administration of DEP at 10 mg/kg was pretreated 2 h before each MPTP administration in DEP3 group and pretreated only in the first MPTP administration day in DEP1 group. As a control, distilled water (DW) was pretreated before each MPTP administration (n = 5 for each of three groups).


RESULTS
In DW group, decreased daily activity counts and increased dysfunction scores were persistently observed for 3 weeks after MPTP. In DEP groups, the similar changes of both levels to those in DW group were temporally observed after MPTP for several days and then the values recovered to the pre-MPTP levels. The results of autoradiography performed after above behavioral observations indicated that markedly lower bindings of [(11)C]PE2I (ligand for dopamine transporters) were observed at the striatum of DW group marmoset as compared with the striatum of additionally prepared MPTP-free marmoset (n = 5). The bindings in DEP groups were almost the same as in the MPTP-free marmoset brains.


CONCLUSIONS
The present preclinical methods using continuous recording of activity of marmosets in their living cages and autoradiography using dopamine transporter ligand might be sensitive for detecting protective actions of drugs for Parkinson's disease.
Ando
Kiyoshi
K
Department of Marmoset Research, Central Institute for Experimental Animals, 1430 Nogawa, Miyamaeku, Kawasaki 216-0001, Japan. ando@ciea.or.jp
Maeda
Jun
J
Inaji
Motoki
M
Okauchi
Takashi
T
Obayashi
Shigeru
S
Higuchi
Makoto
M
Suhara
Tetsuya
T
Tanioka
Yoshikuni
Y
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D002144:Callithrix; D002421:Caudate Nucleus / Q000187:drug effects / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects; D004334:Drug Administration Schedule; D005260:Female; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009048:Motor Skills / Q000187:drug effects; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D004856:Postural Balance / Q000187:drug effects; D011292:Premedication; D011699:Putamen / Q000187:drug effects / Q000473:pathology; D011869:Radioligand Assay; D012642:Selegiline / Q000494:pharmacology*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology
D000978:Antiparkinson Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D012642:Selegiline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine