Acute D2/D3 dopaminergic agonism but chronic D2/D3 antagonism prevents NMDA antagonist neurotoxicity

Biological Psychiatry
Nuri B FarberKevin K Noguchi

Abstract

Antagonists of the N-methyl-D-aspartate (NMDA) glutamate receptor, most likely by producing disinhibtion in complex circuits, acutely produce psychosis and cognitive disturbances in humans, and neurotoxicity in rodents. Studies examining NMDA Receptor Hypofunction (NRHypo) neurotoxicity in animals, therefore, may provide insights into the pathophysiology of psychotic disorders. Dopaminergic D2 and/or D3 agents can modify psychosis over days to weeks, suggesting involvement of these transmitter system(s). We studied the ability of D2/D3 agonists and antagonists to modify NRHypo neurotoxicity both after a one-time acute exposure and after chronic daily exposure. Here we report that D2/D3 dopamine agonists, probably via D3 receptors, prevent NRHypo neurotoxicity when given acutely. The protective effect with D2/D3 agonists is not seen after chronic daily dosing. In contrast, the antipsychotic haloperidol does not affect NRHypo neurotoxicity when given acutely at D2/D3 doses. However, after chronic daily dosing of 1, 3, or 5 weeks, haloperidol does prevent NRHypo neurotoxicity with longer durations producing greater protection. Understanding the changes that occur in the NRHypo circuit after chronic exposure to dopaminergic agents ...Continue Reading

References

May 1, 1992·Journal of Neurochemistry·B K Yamamoto, S Davy
Oct 1, 1991·The American Journal of Psychiatry·D C Javitt, S R Zukin
Dec 6, 1991·Science·J W OlneyM A Sesma
Apr 1, 1991·The American Journal of Psychiatry·S L SatelF H Gawin
Mar 26, 1990·Neuroscience Letters·M Dragunow, R L Faull
Jan 12, 1990·Science·H L Allen, L L Iversen
Mar 1, 1989·Canadian Journal of Anaesthesia = Journal Canadien D'anesthésie·D L Reich, G Silvay
Dec 1, 1989·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·A Kurumaji, J McCulloch
Oct 1, 1973·The American Journal of Psychiatry·E H EllinwoodL M Nelson
Jul 1, 1973·Archives of General Psychiatry·D S Bell
Feb 1, 1982·Anesthesiology·P F WhiteA J Trevor
Dec 1, 1995·Archives of General Psychiatry·J W Olney, N B Farber
Jul 1, 1995·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·N B FarberJ W Olney
Jan 1, 1993·Journal of Neural Transmission. General Section·N WatersA Carlsson
Jul 1, 1993·Biological Psychiatry·N B FarberJ W Olney
Aug 1, 1995·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·A C LahtiC A Tamminga
Feb 1, 1997·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·V Jevtović-TodorovićJ W Olney
Jun 27, 1997·Brain Research·P W Kalivas, P Duffy
Dec 31, 1997·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·N B FarberJ W Olney
Aug 27, 1999·Psychopharmacology·J H KrystalD S Charney
Dec 15, 2000·Progress in Neurobiology·T M Tzschentke
Jun 20, 2001·The Journal of Clinical Psychiatry·J RabinowitzM Davidson
Sep 22, 2001·Neuroscience and Biobehavioral Reviews·N M RichtandS M Strakowski
Oct 30, 2001·Journal of Addictive Diseases·K W Sax, S M Strakowski
Jan 23, 2002·Molecular Psychiatry·N B FarberC Heinkel
Mar 27, 2002·Nature Neuroscience·Jeffrey S Diamond
Oct 11, 2002·Proceedings of the National Academy of Sciences of the United States of America·C Robert Cloninger
Mar 11, 2003·The Journal of Pharmacology and Experimental Therapeutics·Gary E DuncanJeffrey A Lieberman
Nov 7, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Naoe OkamuraMasaomi Iyo
Dec 20, 2003·Annals of the New York Academy of Sciences·Nuri B Farber
May 3, 2005·The American Journal of Psychiatry·Shitij KapurBarry Jones

❮ Previous
Next ❯

Citations

Mar 16, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Xavier López-GilAlbert Adell
Sep 8, 2009·Molecular Pain·Bai-Chuang Shyu, Brent A Vogt

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antipsychotic Drugs

Antipsychotic drugs are a class of medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia and bipolar disorder. Discover the latest research on antipsychotic drugs here