NMDA receptors modulate long-term habituation to spatial novelty: Dose- and genotype-dependent differential effects of posttrial MK-801 and CPP in rats

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Abstract

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 5mg/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. © 1993.

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Pellicano, M. P., Siciliano, F., & Sadile, A. G. (1993). NMDA receptors modulate long-term habituation to spatial novelty: Dose- and genotype-dependent differential effects of posttrial MK-801 and CPP in rats. Physiology and Behavior, 54(3), 563–568. https://doi.org/10.1016/0031-9384(93)90250-J

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