NMDA receptor antagonism impairs reversal learning in developing rats.
Four experiments examined the effect of dizocilpine maleate (MK-801), a noncompetitive N-methyl-Daspartate (NMDA) receptor antagonist, on reversal learning during development. On postnatal days (PND) 21, 26, or 30, rats were trained on spatial discrimination and reversal in a T-maze. When MK-801 was administered (intraperitoneally) before both acquisition and reversal, 0.18 mg/kg generally impaired performance, whereas doses of 0.06 mg/kg and 0.10 mg/kg, but not 0.03 mg/kg, selectively impaired reversal learning (Experiments 1 and 3). The selective effect on reversal was not a result of sensitization to the second dose of MK-801 (Experiment 2) and was observed when the drug was administered only during reversal in an experiment addressing state-dependent learning (Experiment 4). Spatial reversal learning is more sensitive to NMDA-receptor antagonism than is acquisition. No age differences in sensitivity to MK-801 were found between PND 21 and 30.
Chadman
Kathryn K
KK
Department of Psychology, University of Delaware, Newark, DE 19716, USA.
Watson
Deborah J
DJ
Stanton
Mark E
ME
D000818:Animals; D000831:Animals, Newborn; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009949:Orientation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology*; D012193:Reversal Learning / Q000187:drug effects / Q000502:physiology*; D014886:Weaning
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate