Y Kimura1,2, J Maeda3, M Yamada3,4, K Takahata3, K Yokokawa3, Y Ikoma5, C Seki3, H Ito6, M Higuchi3, T Suhara3. 1. Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan. kimura.yasuyuki@qst.go.jp. 2. Department of Clinical and Experimental Neuroimaging Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu, Japan. kimura.yasuyuki@qst.go.jp. 3. Department of Functional Brain Imaging Research, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan. 4. Precursory Research for Embryonic Science and Technology, Japan Science and Technology Agency, Saitama, Japan. 5. Department of Molecular Imaging and Theranostics, National Institute of Radiological Sciences National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan. 6. Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan.
Abstract
RATIONALE: The beneficial effects of psychostimulant drugs in the treatment of psychiatric disorders occur because they increase the extracellular dopamine concentration by inhibiting re-uptake of extracellular dopamine at dopamine transporters. However, the psychological effects at low dopamine transporter occupancy have not been well demonstrated. OBJECTIVES: The purpose of the study was to evaluate the psychological effects, dopamine transporter occupancy, and dopamine release induced by a single oral administration of a clinical dose of mazindol. METHODS: Ten healthy male volunteers were orally administered a placebo and a clinical dose of mazindol (1.5 mg) on separate days. The psychological effects of mazindol were assessed using a visual analogue scale to detect alterations in the state of consciousness. The amount of blockade of dopamine transporters was assessed using positron emission tomography with [18F]FE-PE2I and extracellular dopamine release was measured as the amount of change in [11C]raclopride binding. RESULTS: Following administration of a clinical dose of mazindol, the dopamine transporters were blocked by 24-25 %, and the binding potential of [11C]raclopride was reduced by 2.8-4.6 %. The differences of a score measuring derealisation and depersonalization associated with a positive basic mood were significantly correlated with the change in the [11C]raclopride binding in the limbic striatum. CONCLUSIONS: A subtle alteration in the state of consciousness was detected with a correlation to the changes in the [11C]raclopride binding, which implies that a subtle alteration in extracellular dopamine concentration in the limbic striatum by a small amount of dopamine transporter occupancy can affect the state of consciousness. TRIAL REGISTRATION HTTPS://UPLOAD.UMIN.AC.JP/CGI-OPEN-BIN/CTR_E/CTR_VIEW.CGI?RECPTNO=R000009703 : UMIN000008232.
RATIONALE: The beneficial effects of psychostimulant drugs in the treatment of psychiatric disorders occur because they increase the extracellular dopamine concentration by inhibiting re-uptake of extracellular dopamine at dopamine transporters. However, the psychological effects at low dopamine transporter occupancy have not been well demonstrated. OBJECTIVES: The purpose of the study was to evaluate the psychological effects, dopamine transporter occupancy, and dopamine release induced by a single oral administration of a clinical dose of mazindol. METHODS: Ten healthy male volunteers were orally administered a placebo and a clinical dose of mazindol (1.5 mg) on separate days. The psychological effects of mazindol were assessed using a visual analogue scale to detect alterations in the state of consciousness. The amount of blockade of dopamine transporters was assessed using positron emission tomography with [18F]FE-PE2I and extracellular dopamine release was measured as the amount of change in [11C]raclopride binding. RESULTS: Following administration of a clinical dose of mazindol, the dopamine transporters were blocked by 24-25 %, and the binding potential of [11C]raclopride was reduced by 2.8-4.6 %. The differences of a score measuring derealisation and depersonalization associated with a positive basic mood were significantly correlated with the change in the [11C]raclopride binding in the limbic striatum. CONCLUSIONS: A subtle alteration in the state of consciousness was detected with a correlation to the changes in the [11C]raclopride binding, which implies that a subtle alteration in extracellular dopamine concentration in the limbic striatum by a small amount of dopamine transporter occupancy can affect the state of consciousness. TRIAL REGISTRATION HTTPS://UPLOAD.UMIN.AC.JP/CGI-OPEN-BIN/CTR_E/CTR_VIEW.CGI?RECPTNO=R000009703 : UMIN000008232.
Authors: Andri C Tziortzi; Suzanne N Haber; Graham E Searle; Charalampos Tsoumpas; Christopher J Long; Paul Shotbolt; Gwenaelle Douaud; Saad Jbabdi; Timothy E J Behrens; Eugenii A Rabiner; Mark Jenkinson; Roger N Gunn Journal: Cereb Cortex Date: 2013-01-02 Impact factor: 5.357
Authors: N D Volkow; G J Wang; M W Fischman; R W Foltin; J S Fowler; N N Abumrad; S Vitkun; J Logan; S J Gatley; N Pappas; R Hitzemann; C E Shea Journal: Nature Date: 1997-04-24 Impact factor: 49.962
Authors: Nandini Nittur; Eric Konofal; Yves Dauvilliers; Patricia Franco; Smaranda Leu-Semenescu; Valérie Cochen De Cock; Clara O Inocente; Sophie Bayard; Sabine Scholtz; Michel Lecendreux; Isabelle Arnulf Journal: Sleep Med Date: 2012-10-01 Impact factor: 3.492