D-2 autoreceptors are not involved in the down-regulation of the striatal dopamine transporter caused by alpha-methyl-p-tyrosine

The mechanisms by which the brain dopamine neuronal transporter is regulate d by chronic alteration of dopamine transmission are not well understood. I t has been shown previously that chronic inhibition of dopamine synthesis d ecreases dopamine transporter (DAT) density and function. The purpose of th e present study was to determine whether these effects involve dopamine D-2 receptors. Chronic treatment with cr-methyl-p-tyrosine decreased binding o f [H-3]mazindol and dopamine release by d-amphetamine. The down-regulation of the DAT by alpha-methyl-p-tyrosine was not altered by co-treatment with a D-2 receptor agonist or antagonist. However, chronic treatment with a D-2 agonist, quinpirole, also decreased mazindol binding and amphetamine-induc ed release of dopamine. The results indicate that chronic inhibition of dop amine synthesis and stimulation of D-2 receptors have similar, but independ ent, effects on DAT binding and function.