NMDA RECEPTORS MODULATE LONG-TERM HABITUATION TO SPATIAL NOVELTY - DOSE-DEPENDENT 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 lo w-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 vehic le IP soon after a 10-min test in a Lat-maze. Retention was tested 1 w eek later. Habituation of activity and defecation score was monitored by the between-test decrement (LTH) in the frequency of comer-crossing s (HA) and rearings (VA), with prevailing cognitive and noncognitive m eaning, 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 faci litates 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 inhib its 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 facilitat e LTH of HA. In conclusion, the dose- and genotype-dependent different ial effects of allosteric and isosteric receptor blockade support the hypothesized modulatory role of NMDA receptors in behavioral plasticit y; and the dissociation between retention of cognitive and noncognitiv e behavioral components suggests that NMDA receptors are involved in t heir parallel processing.