Effect of intermittent subchronic MK-801 administration on dopamine synthesis capacity and responsiveness in the prefrontal cortex.

Publisher: John Wiley & Sons, Inc Country of Publication: United States NLM ID: 101719700 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2574-173X (Electronic) Linking ISSN: 2574173X NLM ISO Abbreviation: Neuropsychopharmacol Rep Subsets: MEDLINE

Original Publication: [Hoboken, NJ] : John Wiley & Sons, Inc., [2018]-

Dizocilpine Maleate*/pharmacology ; Dizocilpine Maleate*/administration & dosage ; Prefrontal Cortex*/drug effects ; Prefrontal Cortex*/metabolism ; Dopamine*/metabolism ; Dopamine*/biosynthesis ; Excitatory Amino Acid Antagonists*/pharmacology ; Excitatory Amino Acid Antagonists*/administration & dosage; Animals ; Male ; Rats ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors ; Receptors, N-Methyl-D-Aspartate/metabolism ; Locomotion/drug effects ; Rats, Sprague-Dawley ; Microdialysis/methods

Aim: The therapeutic potential of N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists, particularly ketamine, in mood disorders, is linked to their modulation of dopamine dynamics in the medial prefrontal cortex (mPFC). However, conflicting effects of distinct NMDAR antagonists, like ketamine and phencyclidine, on mPFC dopamine levels stem from variances in their receptor affinity profiles. This study investigates the impact of intermittent subchronic administration of an NMDAR antagonist on dopamine synthesis capacity and responsiveness within the mPFC, focusing on Dizocilpine (MK-801), a highly selective NMDAR antagonist.
Methods: In vivo microdialysis and high-performance liquid chromatography assessed extracellular dopamine levels in the mPFC following subchronic MK-801 treatment. Locomotor activity was measured using a computed video tracking system.
Results: Intermittent subchronic MK-801 administration, followed by a 24-h withdrawal, preserved both dopamine synthesis capacity and responsiveness to MK-801 challenge in the mPFC. However, altered locomotor activity was observed, deviating from previous findings indicating impaired dopamine synthesis and responsiveness in the mPFC with twice-daily subchronic NMDAR antagonist treatment.
Conclusion: These findings offer crucial biochemical insights into the diverse impacts of NMDAR antagonists on dopamine dynamics and the distinct therapeutic mechanisms associated with ketamine in depression treatment. However, further investigation is imperative to pinpoint potential inconsistencies stemming from variances in drug type, dosage, or administration frequency.
(© 2024 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

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20K03483 Japan Society for the Promotion of Science

Keywords: MK‐801; NMDAR antagonists; dopamine; medial prefrontal cortex; subchronic

6LR8C1B66Q (Dizocilpine Maleate)
VTD58H1Z2X (Dopamine)
0 (Excitatory Amino Acid Antagonists)
0 (Receptors, N-Methyl-D-Aspartate)

Date Created: 20240220 Date Completed: 20240603 Latest Revision: 20240605

20240605

PMC11144610

10.1002/npr2.12420

38376999