Summary
N-[methyl-11C] nicotine (11C-nicotine) was given intravenously to monkeys and the uptake and regional distribution of radioactivity was followed in the brain using positron emission tomography (PET). The11C-radioactivity in the brain peaked within 1–2 min and then rapidly declined. Pretreatment with unlabelled nicotine (10 μg/kg) reduced the uptake of11C-radioactivity to the brain by 30%. The uptake of radioactivity was higher following (+)11C-nicotine than (−)11C-nicotine. Both enantiomers were distributed in a similar manner within the brain. When animals were infused with a peripheral nicotinic blocker (trimetaphan) the uptake of radioactivity to the brain was lower following (+)11C-nicotine compared to (−)11C-nicotine. The amount of radioactivity was high in the occipital cortex, thalamus, intermediate in the frontal cortex and low in white matter in (−)11C injected monkeys while no regional difference in distribution of11C-radioactivity was observed after injection of (+)11C-nicotine.
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References
Adem A (1987) Characterization of muscarinic and nicotinic receptors in neural and nonneural tissue: changes in Alzheimer's disease. Acta Univ Upsal 32: 4–61
Adem A, Nordberg A (1988) Nicotinic cholinergic receptor heterogeneity in mammalian brain. In: Rand MJ, Thurau K (eds) The pharmacology of nicotine. IRL Press, Oxford, pp 227–248
Adem A, Synnergren B, Botros M, Öhman B, Winblad B, Nordberg A (1987)3H-acetylcholine nicotinic recognition sites in human brain: characterization of agonist binding. Neurosci Lett 83: 298–302
Adem A, Gillberg PG, Singh Jossan S, Sara V, Nordberg A (1988a) Quantitative autoradiography of nicotinic receptors in large cryosections of human brain hemispheres. Neurosci Lett, in press
Adem A, Singh Jossan S, d'Argy R, Brandt I, Winblad B, Nordberg A (1988b) Distribution of nicotinic receptors in human thalamus as visualized by3H-nicotine and3H-acetylcholine receptor autoradiography. J Neural Transm 73: 77–83
Appelgren LE, Hansson E, Schmiterlöw CG (1962) The accumulation and metabolism of C14-labelled nicotine in brain of mice and cats. Acta Physiol Scand 56: 249–257
Benwell MEM, Balfour DJK, Anderson JM (1988) Evidence that tobacco smoking increases the density of (−)3H-nicotine binding sites in human brain. J Neurochem 50: 1243–1247
Clarke PBS, Pert C, Pert A (1984) Autoradiographic distribution of nicotine receptors in rat brain. Brain Res 323: 390–395
Clarke PBS, Schwartz RD, Paul SM, Pert C, Pert A (1985) Nicotine binding in rat brain: autoradiographical comparison of (3H)-acetylcholine, (3H)-nicotine and125I-alpha-bungarotoxin. J Neurosci 5: 1307–1315
Eriksson L, Bohm C, Kesselberg M, Blomquist G, Litton J, Widén L, Bergström M, Eriksson K, Greitz T (1982) A form ring positron camera for emission tomography of the brain. IEEE Trans Nuclear Sci 29: 539–543
Greitz T, Ingvar DH, Widén L (eds) (1985) The metabolism of the human brain studied with Positron Emission Tomography. Raven Press, New York
Hayaishi O, Torizuka K (eds) (1986) Biomedical imaging Academic Press, New York
Hartvig P, Eckernäs S-Å, Ekblom B, Lindström L, Lundqvist H, Axelsson S, Fasth KJ, Gullberg P, Långström B (1988) Receptor binding and selectivity of three11C-labelled dopamine receptor antagonists in the brain of Rhesus monkey studies with positron emission tomography (PET). Acta Neurol Scand 77: 314–321
Härfstrand A, Adem A, Fuxe K, Agnati L, Andersson K, Nordberg A (1988) Topographical distribution of nicotinic receptors in the rat tel-and diencephalon-quantitative receptor autoradiography using3H-acetylcholine,125I-α-bungarotoxin and3H-nicotine. Acta Physiol Scand 132: 1–14
Jacob P (1982) Resolution of (+)-5-bromonornicotine. Synthesis of (R)-and (S)-nornicotine of high enantiomeric purity. Org Chem 47: 4165–4167
Larsson C (1985) Nicotinic receptors in the central nervous system: methodological and functional aspects. Acta Univ Upsal 104: 4–45
Larsson C, Nordberg A (1985) Comparative analysis of nicotine-like receptor ligand interactions in rodent brain homogenate. J Neurochem 45: 24–31
Larsson C, Lundberg P-Å, Halén A, Adem A, Nordberg A (1987) In vitro binding of3H-acetylcholine to nicotinic receptors in rodent and human brain. J Neural Transm 69: 3–18
Larsson C, Nilsson L, Halén A, Nordberg A (1986) Subchronic treatment of rats with nicotine: effects on tolerance and on3H-acetylcholine and3H-nicotine binding in the rat. Alcohol Drug Depend 17: 37–45
London ED, Waller SB, Wamsley JK (1984) Autoradiographic localization of (3H)-nicotine binding sites in the rat brain. Neurosci Lett 53: 179–184
Långström B, Antoni G, Halldin C, Svärd H, Bergson G (1982) The synthesis of some11C-labelled alkaloids. Chemica Scripta 20: 46–48
Långström B, Halldin C, Antoni G, Gullberg P, Malmborg P, Någren K, Rimland A, Svärd H (1987) Synthesis of11C-L and D-methionine. J Nucl Med 28: 1037–1040
Långström B, Lundkvist H (1979) A flow radioliquid chromatography detector. Radiochem Radioanal Lett 41: 375
Mangan GL, Golding JF (1984) The psychopharmacology of smoking. Cambridge University Press, Cambridge, U.K.
Martin BR, Tripathi HL, Aceto MD, May EL (1983) Relationship of the biodisposition of the stereoisomers of nicotine in the central nervous system to their pharmacological actions. J Pharmacol Exp Ther 226: 157–163
Maziere M, Berger G, Masse R, Phimmer D, Comar D (1979) The “in vivo” distribution of carbon-11 labelled (−)nicotine in animals a method suitable for use in man. In: Remond A, Izard C (eds) Electrophysiological effects of nicotine. Elsevier/North Holland Biomedical Press, Amsterdam, pp 31–47
Nordberg A, Winblad B (1986) Reduced number of (3H) nicotine and (3H) acetylcholine binding sites in the frontal cortex of Alzheimer brains. Neurosci Lett 72: 115–119
Nordberg A, Adem A, Hardy J, Winblad B (1988a) Change in nicotonic receptor subtypes in temporal cortex of Alzheimer brains. Neurosci Lett 86: 317–321
Nordberg A, Adem A, Nilsson L, Romanelli L, Zhang X (1988b) Heterogenous cholinergic nicotinic receptors in the CNS. In: Clementi F et al (eds) Nicotinic acetylcholine receptors in the nervous system. Springer, Berlin Heidelberg New York Tokyo, pp 331–350
Nordberg A, Adem A, Nilsson L, Winblad B (1988c) Nicotinic and muscarinic cholinergic receptor heterogeneity in human brain at normal aging and dementia of Alzheimer type. In: Pepeu G et al (eds) New trends in aging. Fidia Research Series, vol 15. Liviana Press, Padova, pp 27–36
Phelps M, Mazziotta I, Schelbert H (eds) (1986) Positron emission tomography and autoradiograph. Raven Press, New York
Romanelli L, Öhman B, Adem A, Nordberg A (1988) Subchronic treatment of rats with nicotine: interconversion of nicotinic receptor subtypes in brain. Eur J Pharmacol 148: 289–291
Schwartz RD (1986) Autoradiographic distribution of high affinity muscarinic and nicotinic cholinergic receptors labelled with (3H)-acetylcholine in rat brain. Life Sci 38: 2111–2119
Schwartz RD, Kellar KJ (1983) Nicotinic cholinergic receptor binding sites in brain: in vivo regulation. Science 220: 214–216
Stålhandske T (1970) Effects of increased liver metabolism of nicotine on its uptake, elimination and toxicity in mice. Acta Physiol Scand 80: 222–234
Whitehouse PJ, Martino AM, Antuono PG, Lowenstein PR, Coyle RT, Price DL, Kellar KJ (1986) Nicotinic acetylcholine binding sites in Alzheimer's disease. Brain Res 371: 146–151
Wonnacott S (1987) Brain nicotine binding sites. Human Toxicol 6: 343–353
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Nordberg, A., Hartvig, P., Lundqvist, H. et al. Uptake and regional distribution of (+)-(R)- and (−)-(S)-N-[methyl-11C]-nicotine in the brains of Rhesus monkey an attempt to study nicotinic receptors in vivo. J Neural Transm Gen Sect 1, 195–205 (1989). https://doi.org/10.1007/BF02248669
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DOI: https://doi.org/10.1007/BF02248669