Studies on dopamine kinetics in rat brain tissue under the influence of morphine.

The effects of several drugs on the kinetics of 14C-dopamine were studied in slices of rat striata in vitro. While morphine (35 muM) did not affect the uptake of 14C-dopamine into the slices, d-amphetamine (50muM) and imipramine (100 muM) strongly inhibited it. Morphine significantly slowed the K+ -induced release of the labelled dopamine; imipramine almost completely blocked it, while amphetamine h had no clear effect. The effect of morphine was dose-dependent and could be inhibited by the narcotic antagonist naloxone. The results demonstrate that each of the drug had a characteristic pattern of effects in our system studied. The inhibitory action of morphine on the dopamine release in vitro probably reflects in vivo symptoms of a central dopamine deficiency in rats (catalepsy, akinesia, muscular rigidity) after morphine application. In further series of experiments, it was studied if the sensitivity of brain dopamine receptors increased after repeated applications of morphine, which induced clear signs of physical dependence. Since chronic morphine treatment did not increase the potency of apomorphine (which directly stimulates dopamine receptors) in inducing stereotyped behavior, it is concluded that an increased sensitivity of dopamine receptors is not necessarily involved in morphine tolerance and dependence.