MK-801 effects on a learned food preference depend’ on dosage: Is it disruption of learning or a conditioned aversion?

Abstract

Three experiments were conducted to determine the effects of the NMD A antagonist MK-801 on the acquisition of a socially mediated learned food preference. Female rats were exposed for 1 h to a novel smelling/tasting food applied to the snout region of an anesthetized cagemate. Prior to the exposure, different groups were injected subcutaneously with different concentrations of MK-801. Food preferences were established by determining subsequent 24- and 48-h intakes of the novel preexposed food and another novel food. MK-801, at all but the lowest concentration (.02 mg/kg), eliminated the learned food preference for the preexposed diet exhibited by unin-jected controls. At the highest dose (.08 mg/kg), animals appeared to be actually avoiding the preexposed food. This interpretation was reinforced by the findings that MK-801 does not produce reduced intake of the preexposed food if the drug is injected 2 h prior to the exposure. Avoidance of the preexposed diet does occur if MK-801 is injected 1 h after the exposure or if a different NMDA antagonist, AP-5, is infused into the ventricles. These data indicate that the conditioned aversion produced by MK-801 may not be due to general peripheral malaise-inducing properties of the drug and that the NMDA system itself may be involved in processes associated with conditioned food aversions. At low concentrations, NMDA antagonists appear to block learning of an appetitive task, whereas, at high concentrations, they appear to facilitate processes associated with conditioned aversions. © 1990, Psychonomic Society, Inc.. All rights reserved.