This project has continued to focus on investigations of the functional status of the serotonin (5-HT) neurotransmitter system in humans using 5_HT-selective agonists (e.g., m-chlorophenylpiperazine (m-CCP), buspirone) and antagonists (e.g., metergoline, ondansetron) as pharmacologic probes. In a collaborative study, a detailed analysis by Dr. T.D. Brewster of migraine-like late-onset headaches that occurred in a subject of younger females receiving m-CCP revealed: (1) headache responses were more frequent in patients with bulimia nervosa that controls; (2) severity of the headaches was related to higher plasma m- CCP plasma concentrations within these subjects; (3) however, as non- bulimic subjects populations had equally high plasma m_CCP concentrations, a state of post-synaptic 5-HT1C supersensitivity in cranial vasculations or other CNS structures may exist in a bulimic subgroup; and (4) a larger proportion of bulimic patients had blunted prolactin (but not cortisol) responses to m-CCP, suggesting a dissociation between the neuroendocrine and headache responses to m-CCP. In laboratory studies related to serotonin, a close structural analog of MPTP, (the dopamine neurotoxin which produces parkinsonism in several species), 2-NH-2-MPTP was found by Dr. Andrews to possess apparent serotonin and norepinephrine neurotoxicity and to lack effects on dopamine. Dr. K. Peter Lesch successfully isolated and sequenced a cDNA for the human 5-HT transport.