Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys

William P. Melega, Michael J. Raleigh, David B. Stout, Antonio A. DeSalles, Simon R Cherry, Matthew Blurton-Jones, Grenvill G. Morton, Sung Cheng Huang, Michael E. Phelps

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Abstract

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 (K(i)) ratio method of right (lesioned) striatum left (unlesioned) striatum values was used to assess changes in striated activity. Striatal FDOPA K(i) 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 FDOPA K(i) 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 desigued to restore normal function in this primate Parkinsonian model.

Original languageEnglish (US)
Pages (from-to)318-329
Number of pages12
JournalExperimental Neurology
Volume141
Issue number2
DOIs
StatePublished - Oct 1996

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1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Haplorhini
Corpus Striatum
Dopamine
Cercopithecus aethiops
fluorodopa F 18
Aggression
Individuality
Positron-Emission Tomography
Primates

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Melega, W. P., Raleigh, M. J., Stout, D. B., DeSalles, A. A., Cherry, S. R., Blurton-Jones, M., ... Phelps, M. E. (1996). Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys. Experimental Neurology, 141(2), 318-329. https://doi.org/10.1006/exnr.1996.0167

Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys. / Melega, William P.; Raleigh, Michael J.; Stout, David B.; DeSalles, Antonio A.; Cherry, Simon R; Blurton-Jones, Matthew; Morton, Grenvill G.; Huang, Sung Cheng; Phelps, Michael E.

In: Experimental Neurology, Vol. 141, No. 2, 10.1996, p. 318-329.

Research output: Contribution to journalArticle

Melega, WP, Raleigh, MJ, Stout, DB, DeSalles, AA, Cherry, SR, Blurton-Jones, M, Morton, GG, Huang, SC & Phelps, ME 1996, 'Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys', Experimental Neurology, vol. 141, no. 2, pp. 318-329. https://doi.org/10.1006/exnr.1996.0167
Melega, William P. ; Raleigh, Michael J. ; Stout, David B. ; DeSalles, Antonio A. ; Cherry, Simon R ; Blurton-Jones, Matthew ; Morton, Grenvill G. ; Huang, Sung Cheng ; Phelps, Michael E. / Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys. In: Experimental Neurology. 1996 ; Vol. 141, No. 2. pp. 318-329.
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abstract = "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 (K(i)) ratio method of right (lesioned) striatum left (unlesioned) striatum values was used to assess changes in striated activity. Striatal FDOPA K(i) 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 FDOPA K(i) 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 desigued to restore normal function in this primate Parkinsonian model.",
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