Increased dopamine release by the autoreceptor antagonist (+)-AJ 76 is Ca2(+)-dependent.

The effects of the preferential autoreceptor antagonist (+)-AJ 76 on dopamine release and metabolism were studied in the brain microdialysis model. The Ca2+ dependence of the effects of (+)-AJ 76 and d-amphetamine were compared. We found that (+)-AJ 76 increased the release and metabolism of dopamine and that the release was saturable. The release of dopamine by (+)-AJ 76 was dependent on extracellular Ca2+. However, the effects of (+)-AJ 76 on dopamine metabolism were independent of extracellular Ca2+. The effects of d-amphetamine on dopamine release and metabolism were independent of Ca2+. We conclude that the dopamine released by (+)-AJ 76 is dependent on neuronal impulse flow and that the dopamine released is of vesicular origin. The effects on dopamine metabolism and release may be exerted via different mechanisms. In contrast, the release and metabolism of dopamine by d-amphetamine were independent of impulse flow and extracellular Ca2+. We suggest that (+)-AJ 76 and d-amphetamine release dopamine from different pools.