title: The NMDA-receptor antagonist MK-801 selectively disrupts reversal learning in rats.
abstract: We tested the hypothesis that inhibition of NMDA-receptors in rats would lead to a selective impairment of reversal learning in a serial reversal task in the Skinner box. Low doses of MK-801 (0.025 and 0.05 mg/kg) did not affect acquisition of the two-lever discrimination, but impaired performance during the first reversal more than during the third reversal. Similar effects were observed during the series of extinction sessions. The high dose (0.1 mg/kg) completely inhibited reversal and extinction learning, as the rats perseverated in pressing the previously rewarded lever(s). We conclude that NMDA receptor blockade leads to a selective impairment in cognitive flexibility, and shows some similarity to transient inactivation of the medial prefrontal cortex in this respect.
authors: Netherlands Institute for Brain Research, Graduate School Neurosciences Amsterdam, Amsterdam, The Netherlands.
authors: Jamilja A J
authors: JA
authors: van der Meulen
authors: Luka
authors: L
authors: Bilbija
authors: Ruud N J M A
authors: RN
authors: Joosten
authors: Jan P C
authors: JP
authors: de Bruin
authors: Matthijs G P
authors: MG
authors: Feenstra
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D012193:Reversal Learning / Q000187:drug effects* / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate