Increased ventral striatal monoaminergic innervation in Tourette syndrome

Background: Excessive striatal dopaminergic innervation is suggested to underlie Tourette syndrome (TS). Prior imaging and postmortem studies yield conflicting data. Methods: The authors used PET with the type 2 vesicular monoamine transporter ligand [11C]dihydrotetrabenazine (DTBZ) to quantify striatal monoaminergic innervation in patients with TS (n = 19) and control subjects (n = 27). Compartmental modeling was used to determine blood to brain ligand transport (K1) and tissue to plasma distribution volume (a measure of ligand binding) during continuous infusion of DTBZ. TS data were compared with control data using predefined regions of interest and on a voxel by voxel basis. Results: There were no significant differences in ligand binding or ligand transport between patients with TS and control subjects in the dorsal striatum. With voxel by voxel analysis, there was increased DTBZ binding in the right ventral striatum. Conclusions: Previously reported differences between patients with TS and control subjects in dorsal striatal dopamine terminal markers may reflect medication-induced regulation of terminal marker expression or be the result of intrinsic differences in striatal dopaminergic synaptic function. Increased right ventral striatal DTBZ binding suggests that abnormal ventral striatal dopaminergic innervation may underlie tics.

[1]  H. L. Wiener,et al.  Chronic L-deprenyl-induced up-regulation of the dopamine uptake carrier. , 1989, European journal of pharmacology.

[2]  A. Braun,et al.  The Functional Neuroanatomy of Tourette's Syndrome: An FDG-PET Study. II: Relationships between Regional Cerebral Metabolism and Associated Behavioral and Cognitive Features of the Illness , 1995, Neuropsychopharmacology.

[3]  H. Singer,et al.  Abnormal dopamine uptake sites in postmortem striatum from patients with tourette's syndrome , 1991, Annals of neurology.

[4]  E. Richardson.  Neuropathological studies of Tourette syndrome. , 1982, Advances in neurology.

[5]  K. Frey,et al.  The vesicular monoamine transporter is not regulated by dopaminergic drug treatments. , 1995, European journal of pharmacology.

[6]  M. Mintun,et al.  Integrated and automated data analysis method for neuronal activation studies using O-15 water PET , 1993 .

[7]  R. Albin,et al.  Striatal presynaptic monoaminergic vesicles are not increased in Tourette’s syndrome , 1999, Neurology.

[8]  M. Ernst,et al.  High presynaptic dopaminergic activity in children with Tourette's disorder. , 1999, Journal of the American Academy of Child and Adolescent Psychiatry.

[9]  R. Kurlan.  Handbook of Tourette's syndrome and related tic and behavioral disorders , 1993 .

[10]  Yun Zhou,et al.  Elevated intrasynaptic dopamine release in Tourette's syndrome measured by PET. , 2002, The American journal of psychiatry.

[11]  Karl J. Friston,et al.  A unified statistical approach for determining significant signals in images of cerebral activation , 1996, Human brain mapping.

[12]  M. Caron,et al.  OCD-Like Behaviors Caused by a Neuropotentiating Transgene Targeted to Cortical and Limbic D1+ Neurons , 1999, The Journal of Neuroscience.

[13]  V. Sossi,et al.  In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease , 2000, Annals of neurology.

[14]  A. Boulton,et al.  Regulation of striatal aromatic L-amino acid decarboxylase: effects of blockade or activation of dopamine receptors. , 1993, European journal of pharmacology.

[15]  M. Torrens.  Co-Planar Stereotaxic Atlas of the Human Brain—3-Dimensional Proportional System: An Approach to Cerebral Imaging, J. Talairach, P. Tournoux. Georg Thieme Verlag, New York (1988), 122 pp., 130 figs. DM 268 , 1990 .

[16]  E Stern,et al.  A functional neuroanatomy of tics in Tourette syndrome. , 2000, Archives of general psychiatry.

[17]  E. Chee,et al.  Volumetric MRI changes in basal ganglia of children with Tourette's syndrome , 1993, Neurology.

[18]  Suzanne N. Haber,et al.  Gilles de la Tourette's syndrome A postmortem neuropathological and immunohistochemical study , 1986, Journal of the Neurological Sciences.

[19]  A. Kelley,et al.  Differential Behavioral Responses to Dopaminergic Stimulation of Nucleus Accumbens Subregions in the Rat , 1997, Pharmacology Biochemistry and Behavior.

[20]  Guy Marchal,et al.  Multimodality image registration by maximization of mutual information , 1997, IEEE Transactions on Medical Imaging.

[21]  K. Berridge,et al.  Fear and Feeding in the Nucleus Accumbens Shell: Rostrocaudal Segregation of GABA-Elicited Defensive Behavior Versus Eating Behavior , 2001, The Journal of Neuroscience.

[22]  M. Robertson,et al.  Tourette syndrome, associated conditions and the complexities of treatment. , 2000, Brain : a journal of neurology.

[23]  S. Haber,et al.  Basal ganglia peptidergic staining in Tourette syndrome. A follow-up study. , 1992, Advances in neurology.

[24]  D. Kuhl,et al.  [3H]methoxytetrabenazine: A high specific activity ligand for estimating monoaminergic neuronal integrity , 1995, Neuroscience.

[25]  G. N. Brito.  A neurobiological model for Tourette syndrome centered on the nucleus accumbens. , 1997, Medical hypotheses.

[26]  J. O. Schenk,et al.  The Striatal Transporter for Dopamine in the Rat May Be Kinetically Up‐Regulated Following 3 Weeks of Withdrawal from Cocaine Self‐Administration , 1994, Journal of neurochemistry.

[27]  K. Berridge,et al.  The Neuroscience of Natural Rewards: Relevance to Addictive Drugs , 2002, The Journal of Neuroscience.

[28]  D. R. Weinberger,et al.  Cerebral morphometric abnormalities in Tourette's syndrome , 1995, Neurology.

[29]  D E Kuhl,et al.  Assessment of Extrastriatal Vesicular Monoamine Transporter Binding Site Density Using Stereoisomers of [11C]Dihydrotetrabenazine , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[30]  S. Smith‐Roe,et al.  Coincident Activation of NMDA and Dopamine D1Receptors within the Nucleus Accumbens Core Is Required for Appetitive Instrumental Learning , 2000, The Journal of Neuroscience.

[31]  B. Peterson,et al.  Reduced basal ganglia volumes in Tourette's syndrome using three‐dimensional reconstruction techniques from magnetic resonance images , 1993, Neurology.

[32]  C. Tanner,et al.  A rating scale for Gilles de la Tourette's syndrome , 1987, Neurology.

[33]  M R Kilbourn,et al.  A simple synthesis of [11C]dihydrotetrabenazine (DTBZ). , 1997, Nuclear medicine and biology.

[34]  D. Pauls.  A complete genome screen in sib pairs affected by Gilles de la Tourette syndrome. The Tourette Syndrome Association International Consortium for Genetics. , 1999, American journal of human genetics.

[35]  R. Koeppe,et al.  Anatomic standardization: linear scaling and nonlinear warping of functional brain images. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[36]  A. Gjedde,et al.  Regulation of DOPA Decarboxylase Activity in Brain of Living Rat , 1995, Journal of neurochemistry.

[37]  A. Antonini,et al.  The metabolic anatomy of Tourette's syndrome , 1997, Neurology.

[38]  C. I. Connolly,et al.  Building neural representations of habits. , 1999, Science.

[39]  Richardson Ep.  Neuropathological studies of Tourette syndrome. , 1982 .

[40]  Reinhard Dengler,et al.  Dopamine transporter binding in Gilles de la Tourette syndrome , 2000, Journal of Neurology.

[41]  D E Kuhl,et al.  Equilibrium versus Compartmental Analysis for Assessment of the Vesicular Monoamine Transporter Using (+)-α-[11C]Dihydrotetrabenazine (DTBZ) and Positron Emission Tomography , 1997, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[42]  J. Hubble,et al.  Aromatic L‐Amino Acid Decarboxylase Activity of Mouse Striatum Is Modulated via Dopamine Receptors , 1993, Journal of neurochemistry.

[43]  M. Trimble,et al.  A volumetric MRI study of Gilles de la Tourette's syndrome , 1997, Neurology.

[44]  A. Anderson,et al.  A functional magnetic resonance imaging study of tic suppression in Tourette syndrome. , 1998, Archives of general psychiatry.

[45]  J. W. Aldridge,et al.  Coding of Serial Order by Neostriatal Neurons: A “Natural Action” Approach to Movement Sequence , 1998, The Journal of Neuroscience.

[46]  V M Haughton,et al.  Abnormal cerebral activation associated with a motor task in Tourette syndrome. , 1998, AJNR. American journal of neuroradiology.