NMDA receptor involvement in spatial delayed alternation in developing rats.
Two experiments examined the effect of the noncompetitive NMDA receptor antagonist, dizocilpine maleate (MK-801), on spatial working memory during development. Rats were trained on spatial delayed alternation (SDA) in a T-maze after ip administration of 0.06 mg/kg MK-801, 0.1 mg/kg MK-801, or saline on postnatal days (P) P23 and P33 (Experiment 1), or following bilateral intrahippocampal administration of 2.5 or 5.0 microg per side MK-801 or saline on P26 (Experiment 2). In Experiment 1, MK-801 dose-dependently impaired SDA learning at both ages. Because the same doses of systemic MK-801 have no effect on T-maze position discrimination learning, impairment of SDA by MK-801 likely reflects disruption of spatial working memory. Both doses of MK-801 abolished acquisition of SDA performance in Experiment 2. Disruption of hippocampal plasticity may account for the effects produced by systemic MK-801 administration. These results confirm and extend earlier lesion studies by implicating plasticity of hippocampal neurons in the ontogeny of spatial delayed alternation.
Watson
Deborah J
DJ
Department of Psychology, University of Delaware, Newark, DE 19716, USA.
Herbert
Mariel R
MR
Stanton
Mark E
ME
D000375:Aging / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013028:Space Perception / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate