NMDA receptors modulate long-term habituation to spatial novelty: dose- and genotype-dependent differential effects of posttrial MK-801 and CPP in rats.
To investigate the role N-methyl-D-aspartate (NMDA) receptors play in behavioral plasticity, adult male rats of the Naples high-(NHE) and low-excitability (NLE) lines, and of a random-bred Sprague-Dawley strain (NRB) received, the noncompetitive (MK-801:0.01 or 2.5 mg/kg) or the competitive (CPP: 0.01 or 5 mg/kg) NMDA receptor antagonists, or vehicle IP soon after a 10-min test in a Làt-maze. Retention was tested 1 week later. Habituation of activity and defecation score was monitored by the between-test decrement (LTH) in the frequency of corner-crossings (HA) and rearings (VA), with prevailing cognitive and noncognitive meaning, respectively, and of fecal boli. (i) In the NLE-rats, low and high doses of MK-801 facilitate LTH of HA, and a high dose of CPP facilitates LTH of HA. (ii) In the NRB-rats, MK-801 facilitates LTH of HA at a low dose and inhibits LTH of VA at a high dose, whereas CPP inhibits LTH of HA at a high dose only. In contrast, (iii) in the NHE-rats, high doses of MK-801 impair LTH of HA, and low doses of CPP facilitate LTH of HA. In conclusion, the dose- and genotype-dependent differential effects of allosteric and isosteric receptor blockade support the hypothesized modulatory role of NMDA receptors in behavioral plasticity; and the dissociation between retention of cognitive and noncognitive behavioral components suggests that NMDA receptors are involved in their parallel processing.
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Dipt. Fisiologia Umana e Funzioni Biologiche Integrate F. Bottazzi, Università di Napoli Federico II, Italy.
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D000818:Animals; D001143:Arousal / Q000187:drug effects* / Q000502:physiology; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D006185:Habituation, Psychophysiologic / Q000187:drug effects* / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009949:Orientation / Q000187:drug effects* / Q000502:physiology; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology; D012931:Social Environment; D013045:Species Specificity; D013826:Theta Rhythm
D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid