Decrease in Human Striatal Dopamine D2 Receptor Density with Age: A PET Study with [11C]Raclopride

The effect of age on human striatal dopamine D2 receptors was investigated with positron emission tomography (PET) using [11C]raclopride as a radioligand. Twenty-one healthy volunteers aged from 20 to 81 years were studied. An equilibrium method was applied and two separate PET scans with different specific activities of [11C]raclopride were performed. The maximal number of receptors (Bmax) and their dissociation constant (Kd) were calculated using Scatchard analysis. There was an age-dependent decline in the Bmax (r = 0.49; p = 0.02) of striatal D2 receptors while the Kd remained unchanged. The results show that there is an age-related loss of striatal D2 receptors, which, together with other changes in the brain nigrostriatal dopaminergic system, may contribute to extrapyramidal symptoms associated with aging.

[1]  S. Stone-Elander,et al.  D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. , 1990, Archives of general psychiatry.

[2]  H Lundqvist,et al.  Monoamine re‐uptake sites in the human brain evaluated in vivo by means of 11C‐nomifensine and positron emission tomography: the effects of age and Parkinson's disease , 1988, Acta neurologica Scandinavica.

[3]  C. Patlak,et al.  Nigrostriatal function in humans studied with positron emission tomography , 1989, Annals of neurology.

[4]  Philip Seeman,et al.  Human brain dopamine receptors in children and aging adults , 1987, Synapse.

[5]  B. Winblad,et al.  Divergent changes in D-1 and D-2 dopamine binding sites in human brain during aging , 1987, Neurobiology of Aging.

[6]  G. Antoni,et al.  The synthesis of 1-11C-labelled ethyl, propyl, butyl and isobutyl iodides and examples of alkylation reactions , 1986 .

[7]  Albert Gjedde,et al.  EFFECTS OF AGE ON DOPAMINE AND SEROTONIN RECEPTORS MEASURED BY POSITRON TOMOGRAPHY IN THE LIVING HUMAN BRAIN , 1985 .

[8]  P. Mcgeer,et al.  Aging and extrapyramidal function. , 1977, Archives of neurology.

[9]  G. Scatchard,et al.  THE ATTRACTIONS OF PROTEINS FOR SMALL MOLECULES AND IONS , 1949 .

[10]  Richard S. J. Frackowiak,et al.  Striatal function in normal aging: Implications for Parkinson's disease , 1990, Annals of neurology.

[11]  M. Folstein,et al.  EFFECTS OF AGE ON DOPAMINE AND SEROTONIN RECEPTORS MEASURED BY POSITRON TOMOGRAPHY IN THE LIVING HUMAN BRAIN , 1984, Science.

[12]  K. Någren,et al.  PET radioligands for dopamine receptors and re-uptake sites: chemistry and biochemistry. , 1992, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology.

[13]  G. Sedvall,et al.  Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. , 1986, Science.

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

[15]  J. De Keyser,et al.  Age‐related changes in the human nigrostriatal dopaminergic system , 1990, Annals of neurology.

[16]  A. Reeves,et al.  Neurologic Signs in Uncomplicated Aging (Senescence) , 1981 .

[17]  Päivi Marjamäki,et al.  Age-dependent decline in human brain dopamine D1 and D2 receptors , 1990, Brain Research.

[18]  L. Farde,et al.  Kinetic Analysis of Central [11C]Raclopride Binding to D2-Dopamine Receptors Studied by PET—A Comparison to the Equilibrium Analysis , 1989, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  J. Kleinman,et al.  Dopamine receptor subtype imbalance in schizophrenia. , 1987, Life sciences.

[20]  J. Joyce,et al.  Basal Ganglia Dopamine Receptor Autoradiography and Age‐related Movement Disorders a , 1988, Annals of the New York Academy of Sciences.

[21]  H Skre,et al.  NEUROLOGICAL SIGNS IN A NORMAL POPULATION , 1972, Acta neurologica Scandinavica.

[22]  J. Links,et al.  In Vivo Measurement of Dopamine Receptors in Human Brain by Positron Emission Tomography Age and Sex Differences a , 1988, Annals of the New York Academy of Sciences.

[23]  J. Rinne.  Muscarinic and dopaminergic receptors in the aging human brain , 1987, Brain Research.

[24]  M. Martres,et al.  Widespread distribution of brain dopamine receptors evidenced with [125I]iodosulpride, a highly selective ligand. , 1985, Science.

[25]  Y. Agid,et al.  Loss of Striatal [76Br]Bromospiperone Binding Sites Demonstrated by Positron Tomography in Progressive Supranuclear Palsy , 1986, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[26]  C. Nahmias,et al.  Central Dopaminergic Pathways in Hemiparkinsonism Examined by Positron Emission Tomography , 1984, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[27]  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.