NMDA Antagonist MK-801 Does Not Interfere With the Use of Spatial Representation in a Familiar Environment.

Abstract

There is disagreement among researchers concerning whether glutamatergic N-methyl-D-aspartate (NMDA) receptors play a role in constructing spatial representations. Therefore, the authors reexamined the effects of the NMDA antagonist on a spatial discrimination task using rats in a water pool. The authors confirmed that MK-801 impaired acquisition of the spatial discrimination task (Experiment 1). When rats were pretrained before drug treatment, MK-801 induced learning deficits in the novel environment but not in the familiar environment (Experiment 2). Moreover, in a familiar environment, MK-801 did not impair spatial learning, even when the task was completely novel for the rats (Experiment 3). These results suggest that NMDA receptors play an important role in the construction of spatial representations but not in the use of them.

Impairment of the anterior thalamic head direction cell network following administration of the NMDA antagonist MK-801

“…As in the case of place cells, the directional signal carried by the HD system also shows consolidation in new environments (Dudchenko and Zinyuk, 2005) and so it would be interesting to determine if this plasticity can be altered by NMDA antagonists. The finding that spatial learning is most impaired by NMDA blockade when the training occurs in an unfamiliar environment (Caramanos & Shapiro, 1994; Uekita & Okaichi, 2005) is consistent with the possibility that the acquisition of a spatial task is dependent on the consolidation of the environment into the neural circuitry supporting spatial behavior.…”

“…Given these deficits, and the common view that the HD cell network contributes to the neural circuitry used for spatial navigation, the next logical question is whether our findings have identified a potential mechanism by which MK-801 causes spatial deficits. In support of this possibility, as presented in Table 3 many behavioral studies report spatial deficits following administration of MK801 at doses equal or greater than the dose at which our effects on the HD system were apparent (e.g., Butelman, 1989; Ward et al, 1990; Uekita & Okaichi, 2005). Even more convincing, some studies testing multiple doses of MK-801 have found spatial deficits at our high dose 0.1 mg/kg but no or reduced effects at our ineffective dose of .05 mg/kg (Filliat & Blanchet, 1995; Van der Staay et al, 2011;Whishaw & Auer, 1989).…”

NMDA blockade inhibits experience-dependent modification of anterior thalamic head direction cells.

“…Our findings, coupled with evi dence that disruption of the HD network is associated with spatial deficits (Aggleton, Hunt, Nagle, & Neave, 1996;Clark et al, 2013;van Groen, Kadish, & Wyss, 2002;Wilton, Baird, Muir, Honey, & Aggleton, 2001), provide a potential mechanism by which NMDA antagonism disrupts spatial behavior. It is notable that some stud ies have found that spatial learning is most impaired by NMDA blockade when the training occurs in an unfamiliar environment (Caramanos & Shapiro, 1994;Uekita & Okaichi, 2005), which is consistent with our findings and the premise that the acquisition of a spatial task is dependent on the consolidation of the novel environment into the neural circuitry supporting spatial behavior.…”

Opposite effects of MK-801 on the expression of food and morphine-induced conditioned place preference in rats

“…In fact, after considering the sensorimotor disturbances caused by MK-801, the impairment of learning almost vanished Saucier et al, 1996;Keith and Galizio, 1997). Moreover, other lines of studies support the idea that MK-801 does not impair the retrieval process (Heale and Harley, 1990;Venable and Kelly, 1990;Uekita and Okaichi, 2005). Most importantly, if there was any effect of MK-801 on memory retrieval, it seems impossible that MK-801 would just impair the retrieval of morphine-related memory, but spare the retrieval of food-related memory.…”