Glutamate receptors in the rat medial prefrontal cortex regulate set-shifting ability.
The authors examined set-shifting abilities in rats injected with antagonists of N-methyl-D-aspartate (NMDA) receptors (MK801) or alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (LY293558) into the medial prefrontal cortex (mPFC). Set-shifting was assessed with a maze-based task requiring a switch between brightness and texture discrimination strategies. Intra-mPFC injection of MK801 prior to training on the 2nd discrimination impaired discrimination strategy acquisition. The MK801-induced deficit was due to increased perseverative responding. AMPA receptor blockade also impaired acquisition of the 2nd discrimination; these impairments were due to more general cognitive deficits. Results suggest that, within the mPFC, both AMPA and NMDA receptors are necessary for set-shifting, and that NMDA receptor hypofunction impairs the capacity to modify existing knowledge or to inhibit responses that are no longer appropriate.
Stefani
Mark R
MR
Department of Psychiatry, Yale University School of Medicine, Veterans Administration Medical Center, West Haven, Connecticut 06516, USA. mark.stefani@yale.edu
Groth
Karyn
K
Moghaddam
Bita
B
D000818:Animals; D003071:Cognition; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D018782:Maze Learning; D017397:Prefrontal Cortex / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014796:Visual Perception
D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D013777:Tetrazoles; D016291:Dizocilpine Maleate; C082309:tezampanel