Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys.
Biochemical and behavioral criteria were established to determine the long-term stability of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced unilateral striatal dopamine deficiency in the vervet monkey. At time points over a 12-month period, post-MPTP striatal dopamine synthesis capacity was indexed with 6-[18F]fluoro-L-DOPA (FDOPA)-positron emission tomography. For the MPTP-treated subjects (n = 4), an intrasubject FDOPA influx rate constant (Ki) ratio method of right (lesioned) striatum/left (unlesioned) striatum values was used to assess changes in striatal activity. Striatal FDOPA Ki ratios differed less than 5% between studies conducted at 1-2, 5-7, and 9-11 months post-MPTP; these results indicated a stable MPTP-induced striatal lesion over this time period. At the 5-7 and 9-11 month time points, behavioral indices of the MPTP-induced deficits were obtained within a species-typical group setting. For three of the four subjects, persistent decrements in motoric, affiliative, and vigilance behavior were observed while the frequency of aggression toward group members was increased. At the 9-11 month time point, one subject showed a 30% improvement in the social measures, indicative of a partial recovery from the MPTP-induced behavioral decrements although its striatal FDOPAKi ratio remained unchanged. Thus, behavioral and noninvasive biochemical methods can provide complementary indices to assess individual differences in sensitivity to MPTP-induced deficits. Both types of data are required to determine lesion stability and, subsequently, the efficacy of interventions designed to restore normal function in this primate Parkinsonian model.
Melega
W P
WP
Department of Molecular and Medical Pharmacology, University of California, Los Angeles School of Medicine 90095-1735, USA.
Raleigh
M J
MJ
Stout
D B
DB
DeSalles
A A
AA
Cherry
S R
SR
Blurton-Jones
M
M
Morton
G G
GG
Huang
S C
SC
Phelps
M E
ME
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes; D007980:Levodopa / Q000378:metabolism*; D008251:Macaca; D008297:Male; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000503:physiopathology; D014055:Tomography, Emission-Computed
D005462:Fluorine Radioisotopes; D007980:Levodopa