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-CPP), buspirone) and antagonists (e.g., metergoline, ondansetron and trazodone) as pharmacologic probes. A major Pharmacological Reviews article published this year from our group summarized arylpiperazine (including m-CPP)-mediated physiological responses such as blood pressure, neuroendocrine measures, temperature, and subjectively-assessed as well as objectively-rated behavioral changes which have been found to be differentially altered in neuropsychiatric patient subgroups. These alterations in responsivity have been found to differ according to dose, time and route of administration of m-CPP. Additional examples of differential responses to other serotonin agonists and antagonists support the concept that humans possess functionally distinct, independently modulated serotonergic subsystems which appear to correspond, at least in part, to the heterogeneous 5-HT binding sites and neuroanatomical subpathways identified in vitro and in vivo in rodents and some other species.
