OPIOID MODULATION OF AMPHETAMINE-STIMULATED DOPAMINE RELEASE AND CONCENTRATION IN RAT STRIATAL SLICES

The effects of morphine and naltrexone on amphetamine-stimulated relea se and total concentration of dopamine (DA) from rat striatal slices i n vitro were examined in this study. Adult male Sprague-Dawley rats we re sacrificed and the striata were dissected, sliced, and then incubat ed 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-1 015). 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 concentra tion. However, neither morphine nor naltrexone alone altered DA concen tration in the media or tissue slices relative to control (no drug add ed). Moreover, neither morphine nor naltrexone at 1, 10, or 100 muM al tered amphetamine-stimulated DA release. However, morphine (1 or 10 mu M) inhibited the amphetamine-stimulated increase in total concentratio n of DA. This effect of morphine was blocked by naltrexone. NSD-1015 a lone or in combination with morphine did not alter amphetamine-stimula ted 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 m orphine. These results indicate that morphine inhibits the amphetamine -stimulated increase in total DA content, but not the amphetamine-stim ulated release of DA.