In the past year, this project has chiefly focused on investigations of the functional status of the serotonin (5-HT) neurotransmitter system in humans using 5-HT-selective agonists and antagonists as pharmacologic probes. Psychophysiologic responses to the 5-HT agonist, m-chlorophenylpiperazine (m-CPP), including blood pressure, neuroendocrine measures, temperature, and subjectively-assessed as well as objectively-rated behavioral changes, have been found to be differentially altered in different neuropsychiatric patient subgroups. Those differences in responsivity have also been found to differ according to dose and route of administration of M-CPP. Many other examples of differential responses to other serotonin agonists and antagonists support the concept that humans as well as other species have functionally different, independently modulated serotonergic subsystems which appear to correspond, at least in part, to the heterogeneous 5-HT binding sites and neuroanatomical subpathways identified in vivo.
