Amphetamine effects on dopamine release and synthesis rate studied in the Rhesus monkey brain by positron emission tomography

• Published in: Journal of Neural Transmission 1997-01, Vol.104 (4-5), p.329-339
• Main Authors: HARTVIG, P, TORSTENSON, R, TEDROFF, J, WATANABE, Y, FASTH, K. J, BJURLING, P, LANGSTRÖM, B
• Format: Article
• Language: English
• Subjects: Amphetamine - pharmacology; Animals; Biological and medical sciences; Brain - diagnostic imaging; Brain - drug effects; Brain - metabolism; Catecholaminergic system; Cerebrovascular Circulation - drug effects; Decarboxylation - drug effects; Dopamine - metabolism; Dopamine Agents - pharmacology; Dopamine Agonists - metabolism; Dopamine Antagonists - metabolism; Female; Levodopa - metabolism; Macaca mulatta; Medical sciences; Medicin och hälsovetenskap; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pharmacology. Drug treatments; Raclopride; Salicylamides - metabolism; Spiperone - analogs & derivatives; Spiperone - metabolism; Tomography, Emission-Computed
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/bf01277655

Positron emission tomography (PET) was used in a multitracer protocol to evaluate D-amphetamine induced effects on dopamine biosynthesis rate and release in propofol anesthetized Rhesus monkeys. L-[beta-11C]DOPA was used as biochemical probe to study the brain dopamine biosynthesis rate whilst dopamine release was followed by the binding displacement of the [11C]-radiolabelled dopamine receptor antagonists, raclopride and N-methylspiperone. Studies were performed with either a constant rate intravenous infusion of D-amphetamine aiming at plasma concentrations of 0.2 to 25 ng/ml or with intravenous bolus doses of 0.1 and 0.4 mg/kg. Decreased binding of the dopamine receptor antagonists was measured in both modes of D-amphetamine administration but notably [11C]N-methylspiperone was less able to sense D-amphetamine induced release of dopamine. At plasma concentrations aimed above 1 ng/ml a levelling off of the binding of [11C]raclopride at 68 +/- 8.1% of the baseline value indicated that displacement was only possible from a fraction of the binding sites. Amphetamine was observed to increase the rate constant for L-[beta-11C]DOPA utilization in the brain. This was most likely due to an acutely induced subsensitivity of presynaptic dopamine receptors. L-[beta-11C]DOPA and [11C]raclopride were found suitable to indicate changes in dopamine synthesis rate and release respectively using PET and can be used to mirror drug-induced changes of brain dopaminergic function.