Small effect of dopamine release and no effect of dopamine depletion on [18F]fallypride binding in healthy humans

Vanessa L. Cropley, Robert B. Innis, Pradeep J. Nathan, Amira K. Brown, Janet L. Sangare, Alicja Lerner, Hoon Ryu Yong, Kelly E. Sprague, Victor W. Pike, Masahiro Fujita

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Molecular imaging has been used to estimate both drug-induced and tonic dopamine release in the striatum and most recently extrastriatal areas of healthy humans. However, to date, studies of drug-induced and tonic dopamine release have not been performed in the same subjects. This study performed positron emission tomography (PET) with [18F]fallypride in healthy subjects to assess (1) the reproducibility of [18F]fallypride and (2) both D-amphetamine-induced and α-methyl-p-tyrosine (AMPT)-induced changes in dopamin release on [18F]fallypride binding in striatal and extrastriatal areas. Subjects underwent [18F]fallypride PET studies at baseline and following oral D-amphetamine administration (0.5 mg/kg) and oral AMPT administration (3 g/70 kg/day over 44 h). Binding potential (BP) (BP ND) of [18F]fallypride was calculated in striatal and extrastriatal areas using a reference region method. Percent change in regional BPND was computed and correlated with change in cognition and mood. Test-retest variability of [18F]fallypride was low in both striatal and extrastriatal regions. D-Amphetamine significantly decreased BPND by 8-14% in striatal subdivisions, caudate, putamen, substantia nigra, medial orbitofrontal cortex, and medial temporal cortex. Correlation between change in BPND and verbal fluency was seen in the thalamus and substantia nigra. In contrast, depletion of endogenous dopamine with AMPT did not effect [18F]fallypride BPND in both striatum and extrastriatal regions. These findings indicate that [18F]fallypride is useful for measuring amphetamine-induced dopamine release, but may be unreliable for estimating tonic dopamine levels, in striatum and extrastriatal regions of healthy humans.

Original languageEnglish (US)
Pages (from-to)399-408
Number of pages10
JournalSynapse
Volume62
Issue number6
DOIs
StatePublished - Jun 2008

Keywords

  • D radioligand
  • D-amphetamine
  • PET
  • Phasic
  • Tonic
  • α-methyl-para-tyrosine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

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