The effect of single and repeated administration of bromocriptine on monoamine metabolism in rat brain and [3H]spiroperidol binding to striatal membranes

Abstract

Administration of a single high dose of bromocriptine decreased synthesis and release of dopamine and serotonin in several brain regions, most notably in the striatum. Bromocriptine modified the kinetics of [³H]spiroperidol binding to striatal membranes, but these changes were not prominent 2 h after injection when modifications of monoamine metabolism were evaluated. After injection of the same dose of bromocriptine daily for 10 days, the decrease in dopamine synthesis persisted, while other aspects of monoamine metabolism, presumably controlled by dopamine autoreceptors, returned to normal values. This adaptation was not caused by decreased blood levels of bromocriptine, since bromocriptine accumulated in plasma after repeated drug administration. This study provides evidence that different aspects of dopamine cell function, presumably controlled by autoreceptors, show different patterns of adaptation after chronic administration of dopamine agonists.