The neurochemical substrate of psychotic reactions may involve an overactivity of certain dopaminergic systems in the brain. Antipsychotic drugs may be therapeutically efficacious because of their prominent post-synaptic dopamine receptor blocking activity and their ability to reduce presynaptic dopamine release. Prolactin release from the anterior pituitary is under tonic inhibitory control by a dopaminergic system in the hypothalamus. Antipsychotic drugs interrupt this inhibition by blocking dopamine neurotransmission, and thus they enhance prolactin secretion both in laboratory animals and in human subjects. There is some evidence that the prolactin response parallels the absorption and metabolism characteristics of antipsychotic drugs and that it reflects their relative clinical potencies. This research proposal is directed toward the elucidation of the prolactin release effect of antipsychotic drugs as "in vivo bioassay" for these drugs in humans. Comparative dose-response curves for a number of antipsychotic drugs will be developed by fully characterizing the complete prolactin response profile in serum over time following parenteral drug administration. These profiles will be compared with other indices of relative drug potencies, to validate this test system. Different oral and parenteral dose forms for certain drugs, including long-acting preparations, will be compared for prolactin release effects. Radioimmunoassays for these drugs will be developed for direct drug-prolactin correlations in serum. The ultimate purpose will be the development of a standardized predictive test for clinical responsiveness to these drugs in psychiatric patients, based on individual patients' prolactin responses to a challenge dose of drug.