Different effect of age on dopamine transporters in the dorsal and ventral striatum of controls and alcoholics

It is generally agreed that there is a deterioration in brain dopamine (DA) system with aging. The role of the mesolimbic DA in brain ethanol reinforcement is well established, with nucleus accumbens (NAC) serving as a major terminal area of this system, whereas dorsal striatum is more associated with motor control. The aim of this study was to compare putative age‐related alterations of dopamine transporters (DAT) in dorsal and ventral striatum of healthy controls and alcoholics. We studied the effect of age on DAT in caudate (NC), putamen (Pu), and nucleus accumbens (NAC) of eight type 1 and 2 alcoholics and 10 healthy controls by using [125I]PE2I as a radioligand for postmortem human whole hemisphere autoradiography. In the type 1 alcoholic group age and DAT density did not correlate significantly with any of the structures studied. The mean densities of DAT declined significantly with age in controls and type 2 alcoholics in dorsal striatum (NC, Pu) (range of correlation coefficient from −0.49 to −0.94), but not statistically significantly in NAC. In type 1 alcoholics the lack of correlation between DAT density and age may indicate a preexisting dopaminergic deficit in this patient group, whereas age‐related decline among type 2 alcoholics resembled that of healthy controls. Furthermore, dorsal striatal DAT may be more vulnerable to age‐related decline than DAT in NAC. This is supported by the notion that DAT in NAC and dorsal striatum have different molecular weights. Synapse 48:205–211, 2003. © 2003 Wiley‐Liss, Inc.

[1]  G. Brüning,et al.  Adaptive changes of dopamine-D2 receptors in rat brain following ethanol withdrawal: a quantitative autoradiographic investigation. , 1992, Alcohol.

[2]  T. Robbins,et al.  Drug addiction: bad habits add up , 1999, Nature.

[3]  J. Kane,et al.  Prevalence of abnormal involuntary movements (“spontaneous dyskinesias”) in the normal elderly , 2004, Psychopharmacology.

[4]  J. B. Justice,et al.  Dopamine depletion in a striatal subregion disrupts performance of a skilled motor task in the rat , 1985, Brain Research.

[5]  A. Glassman Cigarette smoking: implications for psychiatric illness. , 1993, The American journal of psychiatry.

[6]  G. Gerhardt,et al.  Clearance of Exogenous Dopamine in Rat Dorsal Striatum and Nucleus Accumbens: Role of Metabolism and Effects of Locally Applied Uptake Inhibitors , 1993, Journal of neurochemistry.

[7]  C. Halldin,et al.  Synthesis of unlabelled, 3H‐ and 125I‐labelled β‐CIT and its ϖ‐fluoroalkyl analogues β‐CIT‐FE and β‐CIT‐FP, including synthesis of precursors , 1996 .

[8]  E. Perry,et al.  Dopamine and nicotinic receptor binding and the levels of dopamine and homovanillic acid in human brain related to tobacco use , 1998, Neuroscience.

[9]  J S Fowler,et al.  Decreases in dopamine receptors but not in dopamine transporters in alcoholics. , 1996, Alcoholism, clinical and experimental research.

[10]  Ulla Ruotsalainen,et al.  Striatal D2 dopamine receptor binding characteristics in vivo in patients with alcohol dependence , 1994, Psychopharmacology.

[11]  J. Tiihonen,et al.  Dopamine-transporter density in nucleus accumbens of type-1 alcoholics , 2000, The Lancet.

[12]  N. Volkow,et al.  Dopamine transporters decrease with age. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[13]  Jari Karhu,et al.  Dopamine transporter and D2-receptor density in late-onset alcoholism , 1999, Psychopharmacology.

[14]  D J Brooks,et al.  Personality correlates of [18F]dopa striatal uptake: results of positron-emission tomography in Parkinson's disease. , 1995, The Journal of neuropsychiatry and clinical neurosciences.

[15]  C. Frith,et al.  Spontaneous involuntary disorders of movement: their prevalence, severity, and distribution in chronic schizophrenics with and without treatment with neuroleptics. , 1982, Archives of general psychiatry.

[16]  E. Wolters,et al.  Imaging of dopamine transporters with [123I]FP‐CIT SPECT does not suggest a significant effect of age on the symptomatic threshold of disease in Parkinson's disease , 2001, Synapse.

[17]  G. Sedvall,et al.  Whole hemisphere autoradiography of the postmortem human brain. , 1998, Nuclear medicine and biology.

[18]  D. Guilloteau,et al.  Visualization of the Dopamine Transporter in the Human Brain Postmortem with the New Selective Ligand [125I]PE2I , 1999, NeuroImage.

[19]  C. Robert Cloninger,et al.  Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. , 1981, Archives of general psychiatry.

[20]  T. J. Breen,et al.  Biostatistical Analysis (2nd ed.). , 1986 .

[21]  J. Tiihonen,et al.  Striatal presynaptic dopamine function in type 1 alcoholics measured with positron emission tomography , 1998, Molecular Psychiatry.

[22]  J. Voogd,et al.  The human central nervous system , 1978 .

[23]  D. Morgan The dopamine and serotonin systems during aging in human and rodent brain. A brief review , 1987, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[24]  A. M. Myers,et al.  Iodine-123-IPT SPECT imaging of CNS dopamine transporters: nonlinear effects of normal aging on striatal uptake values. , 1996, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[25]  J. Holden,et al.  Age‐dependent decline of dopamine D1 receptors in human brain: A PET study , 1998, Synapse.

[26]  J. Kleinman,et al.  Decreased density of human striatal dopamine uptake sites with age. , 1986, European Journal of Pharmacology.

[27]  I. Creese,et al.  Effect of Chronic Nicotine Treatment and Withdrawal on Rat Striatal D1 and D2 Dopamine Receptors , 1992, The Journal of pharmacy and pharmacology.

[28]  M. Kuhar,et al.  Dopamine transporters in the nucleus accumbens and the striatum have different apparent molecular weights , 1991, Synapse.

[29]  S. Shapiro,et al.  A Comparative Study of Various Tests for Normality , 1968 .

[30]  J. Karhu,et al.  Pharmacokinetics and dosimetry of iodine-123 labelled PE2I in humans, a radioligand for dopamine transporter imaging , 1998, European Journal of Nuclear Medicine.

[31]  M. Kuhar,et al.  [3H]cocaine binding and inhibition of [3H]dopamine uptake is similar in both the rat striatum and nucleus accumbens. , 1989, European journal of pharmacology.

[32]  L. Golbe,et al.  Dopamine‐related personality traits in Parkinson's disease , 1993, Neurology.

[33]  Jari Karhu,et al.  Altered striatal dopamine re-uptake site densities in habitually violent and non-violent alcoholics , 1995, Nature Medicine.

[34]  C. Cloninger The psychobiological regulation of social cooperation , 1995, Nature Medicine.

[35]  J S Fowler,et al.  Decreased dopamine transporters with age in healthy human subjects , 1994, Annals of neurology.

[36]  J. Tiihonen,et al.  Mortality of antisocial male criminals , 2001 .

[37]  M. Drake Diagnostic and Statistical Manual of Mental Disorders (3rd ed. rev.) , 1988 .

[38]  P. Garris,et al.  Different effects of cocaine and nomifensine on dopamine uptake in the caudate-putamen and nucleus accumbens. , 1995, The Journal of pharmacology and experimental therapeutics.

[39]  Jacob Cohen A Coefficient of Agreement for Nominal Scales , 1960 .

[40]  J. Marshall,et al.  Movement disorders of aged rats: reversal by dopamine receptor stimulation. , 1979, Science.

[41]  Y. Itoyama,et al.  Effect of aging on dopaminergic receptors and uptake sites in the rat brain studied by receptor autoradiography , 1997, Journal of the Neurological Sciences.

[42]  Takashi Kato,et al.  Age‐related changes of dopamine D1‐like and D2‐like receptor binding in the F344/N rat striatum revealed by positron emission tomography and in vitro receptor autoradiography , 2001, Synapse.

[43]  P. Garris,et al.  Preferential Increases in Nucleus Accumbens Dopamine after Systemic Cocaine Administration Are Caused by Unique Characteristics of Dopamine Neurotransmission , 2000, The Journal of Neuroscience.

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

[45]  D. Guilloteau,et al.  Synthesis and Ligand Binding of Nortropane Derivatives: N‐Substituted 2β‐Carbomethoxy‐3β‐(4′‐iodophenyl)nortropane and N‐(3‐ Iodoprop‐(2E)‐enyl)‐2β‐carbomethoxy‐3β‐(3′,4′‐disubstituted phenyl)nortropane. New High‐Affinity and Selective Compounds for the Dopamine Transporter. , 1997 .

[46]  D. Segal,et al.  Differential effects of amphetamine and dopamine uptake blockers (cocaine, nomifensine) on caudate and accumbens dialysate dopamine and 3-methoxytyramine. , 1992, The Journal of pharmacology and experimental therapeutics.

[47]  J. Tiihonen,et al.  Dopamine D2/D3-receptor and transporter densities in nucleus accumbens and amygdala of type 1 and 2 alcoholics , 2001, Molecular Psychiatry.