The effects of morphine and naltrexone on amphetamine-stimulated release and total concentration of dopamine (DA) from rat striatal slices in vitro were examined in this study. Adult male Sprague-Dawley rats were sacrificed and the striata were dissected, sliced, and then incubated in buffer solution at 37 degrees C with amphetamine in the presence or absence of various concentrations of morphine, naltrexone (or both), or the dihydroxyphenylalanine (DOPA) decarboxylase inhibitor (NSD-1015). The concentrations of DOPA, DA, and dihydroxyphenylacetic acid (DOPAC) in the tissue slices and buffer media were measured by HPLC/EC. Amphetamine enhanced DA release and also increased total DA concentrations. However, neither morphine nor naltrexone alone altered DA concentration in the media or tissue slices relative to control (no drug added). Moreover, neither morphine nor naltrexone at 1, 10, or 100 microM altered amphetamine-stimulated DA release. However, morphine (1 or 10 microM) inhibited the amphetamine-stimulated increase in total concentration of DA. This effect of morphine was blocked by naltrexone. NSD-1015 alone or in combination with morphine did not alter amphetamine-stimulated DA release, but significantly reduced DA concentration in striatal slices. NSD-1015 alone also increased DOPA accumulation in both media and tissue slices, and this effect was inhibited by the addition of morphine. These results indicate that morphine inhibits the amphetamine-stimulated increase in total DA content, but not the amphetamine-stimulated release of DA.