Dopamine D4 receptors modulate brain metabolic activity in the prefrontal cortex and cerebellum at rest and in response to methylphenidate.

The European Journal of Neuroscience
Michael MichaelidesPanayotis K Thanos

Abstract

Methylphenidate (MP) is widely used to treat attention deficit hyperactivity disorder (ADHD). Variable number of tandem repeats polymorphisms in the dopamine D4 receptor (D(4)) gene have been implicated in vulnerability to ADHD and the response to MP. Here we examined the contribution of dopamine D4 receptors (D4Rs) to baseline brain glucose metabolism and to the regional metabolic responses to MP. We compared brain glucose metabolism (measured with micro-positron emission tomography and [(18)F]2-fluoro-2-deoxy-D-glucose) at baseline and after MP (10 mg/kg, i.p.) administration in mice with genetic deletion of the D(4). Images were analyzed using a novel automated image registration procedure. Baseline D(4)(-/-) mice had lower metabolism in the prefrontal cortex (PFC) and greater metabolism in the cerebellar vermis (CBV) than D(4)(+/+) and D(4)(+/-) mice; when given MP, D(4)(-/-) mice increased metabolism in the PFC and decreased it in the CBV, whereas in D(4)(+/+) and D(4)(+/-) mice, MP decreased metabolism in the PFC and increased it in the CBV. These findings provide evidence that D4Rs modulate not only the PFC, which may reflect the activation by dopamine of D4Rs located in this region, but also the CBV, which may reflect a...Continue Reading

References

Dec 1, 1976·Experimental Neurology·R S SniderS R Snider
May 1, 1992·The American Journal of Psychiatry·N D VolkowF Henn
Nov 15, 1990·The New England Journal of Medicine·A J ZametkinR M Cohen
May 23, 1995·Proceedings of the National Academy of Sciences of the United States of America·N C AndreasenR D Hichwa
Jun 1, 1993·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·J A MatochikA J Zametkin
Sep 15, 1995·European Journal of Pharmacology·F E PontieriF Orzi
Feb 1, 1996·Brain : a Journal of Neurology·O GodefroyM Rousseaux
Jul 1, 1996·Archives of General Psychiatry·F X CastellanosJ L Rapoport
Mar 1, 1996·Journal of the American Academy of Child and Adolescent Psychiatry·M H TeicherN I Barber
Oct 29, 1996·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·P S Goldman-Rakic
Mar 1, 1997·Journal of the American Academy of Child and Adolescent Psychiatry·B J CaseyJ L Rapoport
Sep 11, 1998·Journal of Child Neurology·S H MostofskyM B Denckla
Nov 25, 1998·Proceedings of the National Academy of Sciences of the United States of America·C J VaidyaJ D Gabrieli
Dec 1, 1999·Molecular Psychiatry·F I Tarazi, R J Baldessarini
Feb 15, 2000·The American Journal of Psychiatry·J B SchweitzerC D Kilts
Mar 25, 2000·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·D S Melchitzky, D A Lewis
Apr 14, 2000·Frontiers in Bioscience : a Journal and Virtual Library·J HimelsteinJ M Halperin
Sep 23, 2000·The Journal of Neuropsychiatry and Clinical Neurosciences·M RapoportH Mayberg
Oct 18, 2000·European Journal of Pharmacology·J N OakH H Van Tol
Dec 29, 2000·Journal of the American Academy of Child and Adolescent Psychiatry·G A SunoharaC L Barr
Mar 20, 2001·Archives of General Psychiatry·F X CastellanosJ L Rapoport
Jul 21, 2001·Annals of the New York Academy of Sciences·J N GieddF X Castellanos
Feb 28, 2002·The European Journal of Neuroscience·Tomás L FalzoneMarcelo Rubinstein
Aug 3, 2002·The American Journal of Psychiatry·Carl M AndersonMartin H Teicher
Apr 18, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Julie B SchweitzerClinton D Kilts

❮ Previous
Next ❯

Citations

Nov 16, 2013·The Journal of Clinical Investigation·Michael MichaelidesYasmin L Hurd
Aug 28, 2014·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Ricarda SchwarzSarah Kittel-Schneider
May 20, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Shunsuke NakazawaJunji Ichihara
Jun 6, 2013·Evidence-based Complementary and Alternative Medicine : ECAM·Jin-Hui LiHong Zhang
Jun 9, 2016·PloS One·Panayotis K ThanosNora D Volkow
Apr 6, 2019·Pharmacogenetics and Genomics·Tyler StevensTeri E Klein
Sep 19, 2015·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Daniel J UrbanBryan L Roth

❮ Previous
Next ❯

Related Concepts

Related Feeds

Attention Disorders

Attention is involved in all cognitive activities, and attention disorders are reported in patients with various neurological diseases. Here are the latest discoveries pertaining to attention disorders.