Intrahippocampal administration of an NMDA-receptor antagonist impairs spatial discrimination reversal learning in weanling rats.
Systemic administration of MK-801, an NMDA-receptor antagonist, impairs reversal learning in weanling rats [Chadman, K.K., Watson, D.J., & Stanton, M.E. (2006). NMDA-receptor antagonism impairs reversal learning in developing rats. Behavioral Neuroscience, 120(5), 1071-1083]. The brain systems responsible for this effect are not known in either adult or young animals. This study tested the hypothesis that hippocampal NMDA receptors are engaged in weanling-age rats during spatial discrimination reversal training in a T-maze. In Experiment 1, 26-day-old Long-Evans rats (P26) showed a dose-related impairment on this task following bilateral intrahippocampal administration of either 2.5 or 5.0microg MK-801 or saline vehicle during the reversal training phase only. In Experiment 2, P26 rats were trained on the same task, but received intrahippocampal MK-801 (2.5microg) during acquisition, reversal, both, or neither. MK-801 failed to impair acquisition, ruling out nonspecific "performance effects" of the drug. MK-801 impaired reversal irrespective of drug treatment during acquisition. NMDA-receptor antagonism in the hippocampus is sufficient to account for the previously reported effects of systemic MK-801 on reversal of T-maze position discrimination.
Watson
Deborah J
DJ
University of Delaware, Department of Psychology, Newark, DE 19716, USA. dwatson@psych.udel.edu
Stanton
Mark E
ME
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002404:Catheterization; D004193:Discrimination Learning / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D005260:Female; D006624:Hippocampus / Q000187:drug effects*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012193:Reversal Learning / Q000187:drug effects*; D013028:Space Perception / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate