title: Modafinil improves performance in the multiple T-Maze and modifies GluR1, GluR2, D2 and NR1 receptor complex levels in the C57BL/6J mouse.
abstract: Modafinil has been shown to modify behavioural and cognitive functions and to effect several brain receptors. Effects, however, were not observed at the receptor protein complex level and it was therefore the aim of the study to train mice in the multiple T-Maze (MTM) as a paradigm for spatial memory and to determine paralleling brain receptor complex levels. Sixty C57BL/6J mice were used in the study and divided into four groups (trained drug injected; trained vehicle injected; yoked drug injected; yoked vehicle injected). Animals obtained training for 4 days and were killed 6 h following the last training session on day 4. Hippocampi were dissected from the brain, membrane fractions were prepared by ultracentrifugation and were run on blue-native gels and immunoblotted with antibodies against major brain receptors. Modafinil treatment led to decreased latency and increased average speed, but not to changes in pathlength and number of correct decisions in the MTM. Drug effects were modifying receptor complexes of GluR1, GluR2, D2 and NR1. Training effects on receptor complex levels were observed for GluR3, D1 and nicotinic acetylcholine receptor alpha 7 (Nic7). GluR1 levels were correlating with GluR2 and D1 levels were correlating with D2 and NR1. Involvement of the glutamatergic, NMDA, dopaminergic and nicotinergic system in modafinil and memory training were herein described for the first time. A brain receptor complex pattern was revealed showing the concerted action following modafinil treatment.
authors.affiliation: Department of Pediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Sunetra
authors.initials: S
authors.lastname: Sase
authors.forename: Deeba
authors.initials: D
authors.lastname: Khan
authors.forename: Fernando
authors.initials: F
authors.lastname: Sialana
authors.forename: Harald
authors.initials: H
authors.lastname: Höger
authors.forename: Nina
authors.initials: N
authors.lastname: Russo-Schlaff
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D007274:Injections, Intraperitoneal; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D000077408:Modafinil; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000378:metabolism*; D018091:Receptors, AMPA / Q000032:analysis / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000032:analysis / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate
chemical_list: D001559:Benzhydryl Compounds; D002352:Carrier Proteins; D000077408:Modafinil; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; C121673:Gprin1 protein, mouse; C104722:glutamate receptor ionotropic, AMPA 2