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

SummaryPositron 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-[β-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 forl-[β-11C]DOPA utilization in the brain. This was most likely due to an acutely induced subsensitivity of presynaptic dopamine receptors.l-[β-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.

[1]  E. Meyer.  Simultaneous correction for tracer arrival delay and dispersion in CBF measurements by the H215O autoradiographic method and dynamic PET. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[2]  P. Seeman,et al.  Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3H]raclopride: Implications for positron emission tomography of the human brain , 1989, Synapse.

[3]  U. Ungerstedt,et al.  In Vivo Measurement of Dopamine and Its Metabolites by Intracerebral Dialysis: Changes After d‐Amphetamine , 1983, Journal of neurochemistry.

[4]  M. Raichle,et al.  Brain blood flow measured with intravenous H2(15)O. I. Theory and error analysis. , 1983, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  J S Fowler,et al.  Striatal binding of the PET ligand 11C‐raclopride is altered by drugs that modify synaptic dopamine levels , 1993, Synapse.

[6]  B. Långström,et al.  L‐DOPA modulates striatal dopaminergic function in vivo: Evidence from PET investigations in nonhuman primates , 1997, Synapse.

[7]  M. Mintun,et al.  Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. , 1983, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[8]  C. Bohm,et al.  Automated blood sampling systems for positron emission tomography , 1988 .

[9]  J S Fowler,et al.  Amphetamine induced decreases in (18F)‐N‐methylspiroperidol binding in the baboon brain using positron emission tomography (PET) , 1991, Synapse.

[10]  B. Långström,et al.  Cerebral uptake and utilization of therapeutic [β‐11C]‐L‐DOPA in Parkinson's disease measured by positron emission tomography. Relations to motor response , 1992, Acta neurologica Scandinavica.

[11]  Yasuyoshi Watanabe,et al.  Enzymatic Synthesis of Carboxy-11C-Labelled L-Tyrosine, L-DOPA, L-Tryptophan and 5-Hydroxy-L-tryptophan. , 1990 .

[12]  P. Verbanck,et al.  Acute amphetamine-induced subsensitivity of A10 dopamine autoreceptors in vitro , 1991, Brain Research.

[13]  P. A. Shore,et al.  Effects of amphetamine and amfonelic acid on the disposition of striatal newly synthesized dopamine. , 1982, European journal of pharmacology.

[14]  Marc Laruelle,et al.  Amphetamine‐stimulated dopamine release competes in vivo for [123I]IBZM binding to the D2 receptor in nonhuman primates , 1992, Synapse.

[15]  F. J. White,et al.  Electrophysiological evidence for A10 dopamine autoreceptor subsensitivity following chronicd-amphetamine treatment , 1984, Brain Research.

[16]  S. Huang,et al.  Weighted Integration Method for Local Cerebral Blood Flow Measurements with Positron Emission Tomography , 1986, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[17]  A. Leshner.  Molecular mechanisms of cocaine addiction. , 1996, The New England journal of medicine.

[18]  G. Rebec,et al.  Long-term amphetamine treatment attenuates or reverses the depression of neuronal activity produced by dopamine agonists in the ventral tegmental area. , 1984, Life sciences.

[19]  R. Mark Wightman,et al.  Hyperlocomotion and indifference to cocaine and amphetamine in mice lacking the dopamine transporter , 1996, Nature.

[20]  B. McMillen.  CNS stimulants: two distinct mechanisms of action for amphetamine-like drugs , 1983 .

[21]  Bengt Långström,et al.  Differential effects of levodopa on dopaminergic function in early and advanced Parkinson's disease , 1997, Annals of neurology.

[22]  Richard S. J. Frackowiak,et al.  Striatal D2 receptor status in patients with Parkinson's disease, striatonigral degeneration, and progressive supranuclear palsy, measured with 11C‐raclopride and positron emission tomography , 1992, Annals of neurology.

[23]  D. Segal,et al.  Concomitant characterization of behavioral and striatal neurotransmitter response to amphetamine using in vivo microdialysis , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[24]  S. Snyder,et al.  Properties of [3H]haloperidol and [3H]dopamine binding associated with dopamine receptors in calf brain membranes. , 1976, Molecular pharmacology.

[25]  G. Arbuthnott,et al.  Amphetamine‐Induced Dopamine Release in the Rat Striatum: An In Vivo Microdialysis Study , 1988, Journal of neurochemistry.

[26]  B. Långström,et al.  Liquid chromatographic analysis of brain homogenates and microdialysates for the quantification of L-[beta-11C]DOPA and its metabolites for the validation of positron emission tomography studies. , 1995, Journal of pharmaceutical and biomedical analysis.

[27]  D. Wong,et al.  Effects of endogenous dopamine on kinetics of [3H]N‐methylspiperone and [3H]raclopride binding in the rat brain , 1991, Synapse.

[28]  G. Antoni,et al.  Synthesis of L- and D-[methyl-11C]methionine. , 1987, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[29]  B. Långström,et al.  Estimation of regional cerebral utilization of [11C]‐L‐3, 4‐dihydroxy‐phenylalanine (DOPA) in the primate by positron emission tomography , 1992, Acta neurologica Scandinavica.

[30]  B. Långström,et al.  Levodopa‐induced changes in synaptic dopamine in patients with Parkinson's disease as measured by [11C]raclopride displacement and PET , 1996, Neurology.

[31]  J. Anderson.  A rapid and accurate method to realign PET scans utilizing image edge information. , 1995, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[32]  B. Långström,et al.  Brain kinetics of L-[Β-11 C]DOPA in humans studied by positron emission tomography , 2005, Journal of Neural Transmission / General Section JNT.

[33]  A. Argiolas,et al.  Evidence for a direct action of amphetamine on dopamine metabolism in the rat substantia Nigra in vivo , 2004, Naunyn-Schmiedeberg's Archives of Pharmacology.

[34]  H. Davis,et al.  Prevention of denervation atrophy in muscle: Mammalian neurotrophic factor is not transferrin , 1984, Brain Research.

[35]  P B Hoffer,et al.  Microdialysis and SPECT measurements of amphetamine‐induced dopamine release in nonhuman primates , 1997, Synapse.