LONGITUDINAL BEHAVIORAL AND 6-[F-18]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 m onkey. At time points over a 12-month period, post-MPTP striatal dopam ine synthesis capacity was indexed with 6-[F-18]fluoro-L-DOPA (FDOPA)- positron emission tomography. For the MPTP-treated subjects (n = 4), a n intrasubject FDOPA influx rate constant (K-i) ratio method of right (lesioned) striatum/left (unlesioned) striatum values was used to asse ss changes in striatal activity. Striatal FDOPA K-i ratios differed le ss 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 o ver this time period. At the 5-7 and 9-11 month time points, behaviora l indices of the MPTP-induced deficits were obtained within a species- typical group setting, For three of the four subjects, persistent decr ements in motoric, affiliative, and vigilance behavior were observed w hile the frequency of aggression toward group members was increased. A t the 9-11 month time point, one subject showed a 30% improvement in t he social measures, indicative of a partial recovery from the MPTP-ind uced behavioral decrements although its striatal FDOPA K-i ratio remai ned unchanged. Thus, behavioral and noninvasive biochemical methods ca n provide complementary indices to assess individual differences in se nsitivity to MPTP-induced deficits. Both types of data are required to determine lesion stability and, subsequently, the efficacy of interve ntions designed to restore normal function in this primate Parkinsonia n model. (C) 1996 Academic Press, Inc.