The effect of modafinil on the rat dopamine transporter and dopamine receptors D1-D3 paralleling cognitive enhancement in the radial arm maze

Frontiers in Behavioral Neuroscience
Yasemin KarabacakGert Lubec

Abstract

A series of drugs have been reported to increase memory performance modulating the dopaminergic system and herein modafinil was tested for its working memory (WM) enhancing properties. Reuptake inhibition of dopamine, serotonin (SERT) and norepinephrine (NET) by modafinil was tested. Sixty male Sprague-Dawley rats were divided into six groups (modafinil-treated 1-5-10 mg/kg body weight, trained and untrained and vehicle treated trained and untrained rats; daily injected intraperitoneally for a period of 10 days) and tested in a radial arm maze (RAM), a paradigm for testing spatial WM. Hippocampi were taken 6 h following the last day of training and complexes containing the unphosphorylated or phosphorylated dopamine transporter (DAT-CC and pDAT-CC) and complexes containing the D1-3 dopamine receptor subunits (D1-D3-CC) were determined. Modafinil was binding to the DAT but insignificantly to SERT or NET and dopamine reuptake was blocked specifically (IC50 = 11.11 μM; SERT 1547 μM; NET 182 μM). From day 8 (day 9 for 1 mg/kg body weight) modafinil was decreasing WM errors (WMEs) in the RAM significantly and remarkably at all doses tested as compared to the vehicle controls. WMEs were linked to the D2R-CC and the pDAT-CC. pDAT and ...Continue Reading

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Citations

Nov 24, 2016·International Journal of Molecular Sciences·Michael De SantisChao Deng
Jul 29, 2021·Journal of Psychopharmacology·David J Heal, Sharon L Smith
Nov 9, 2017·ACS Chemical Neuroscience·Eric Murillo-RodríguezSérgio Machado
Aug 17, 2021·Journal of Clinical Pharmacology·James R Docherty, Hadeel A Alsufyani

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Methods Mentioned

BETA
Electrophoresis
protein assay
Assay

Software Mentioned

Image J
GraphPad
GraphPad Prism

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