Activation of AMPA/kainate glutamatergic receptors in the nucleus accumbens may be a component of the mechanism of drug induced reward. To test this hypothesis, 6,7-dinitroquinoxaline-2,3-dione (DNQX), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)/kainate glutamatergic receptor anatagonist, was injected into the nucleus accumbens before the administration of amphetamine or morphine during the training phase (acquisition) of a conditioned place preference paradigm. Rats were then tested for place preference in the absence of drugs. In other experiments, DNQX was given before testing for place preference (expression) but not during the training phase. Bilateral injection of DNQX (1 microgram/0.5 microliters/side) inhibited acquisition of place preference to amphetamine (1 mg/kg) but not morphine (10 mg/kg). During acquisition, DNQX marginally attenuated the locomotor stimulation elicited by amphetamine during the first but not subsequent training sessions, while the combination of morphine plus DNQX produced marked akinesia during each training session. When given prior to testing, DNQX inhibited the expression of place preference induced by amphetamine and morphine but did not affect locomotor activity. The results suggest that activation of AMPA/kainate receptors is involved in the primary reward stimulation (acquisition of place preference) of amphetamine but not morphine and in behaviors elicited by memory of primary reward stimulation (expression of place preference) for both drugs. Furthermore, locomotor activity during conditioning is not necessary for acquisition of place preference.