Pharmacologically induced N-methyl-D-aspartate receptor hypofunction impairs goal-directed food seeking in rats.

Abstract

AIM\nAcute N-methyl-D-aspartate (NMDA) receptor antagonism is an important pharmacological animal model of schizophrenia. In previous studies, schizophrenia patients show impaired goal-directed behavior in an outcome-specific devaluation procedure. In this study, we investigated whether the rat model of the NMDA receptor blockade also showed altered goal-directed behavior in a satiety-induced outcome devaluation paradigm.\n\n\nMETHODS\nIn experiments 1 and 2, we aimed to establish the satiety-induced outcome devaluation test using sucrose and lipid rewards in operant conditioning and free consumption paradigms. In experiment 3, we tested the effect of MK-801 (0.1\xa0mg/kg, i.p.) on outcome-specific devaluation.\n\n\nRESULTS\nExperiments 1 and 2 demonstrated that 1-h ad libitum food consumption is sufficient to induce outcome-specific devaluation in both lever-press and free consumption tests in rats. Experiment 3 showed that the administration of MK-801 impaired satiety-induced devaluation in the lever-press test but not in the subsequent free consumption test.\n\n\nCONCLUSIONS\nOur results suggest that acute pharmacological NMDA receptor antagonism in rats is a useful animal model for impaired goal-directed behavior in schizophrenia.