BIOL PSYCHIATRY 1992;32:1055-1061 1055 Effect of m-Chlorophenylpiperazine on Plasma Homovanillic Acid Concentrations in Healthy Subjects Ren6 S. Kahn, Peter Knott, Steven Gabriel, Kimberly DuMont, Lisa Mastroianni, and Michael Davidson In view of the abundant anatomical and functional interactions between serotonin and dopamine systems, this study examined the effect of the serotonin agonist, m.chloro. phenylpiperazine (mCPP) on plasma concentrations of the dopamine metabolite, homo- vanillic acid. Plasma prolactin levels, body temperature, and mCPP blood level were also measured, mCPP (0.35 mg/kg) and placebo were administered orally to 10 healthy men in a randomized double-blind design. Variables were measured for 210 rain after administration of capsules, mCPP raised prolactin and temperature as compared to placebo, but did not affec~plasma homovaniilic acid concentrations. Results suggest that mCPP does not alter dopamine function. Introduction m-Chlorophenylpiperazine (mCPP) is a serotonin (5-hydroxytryptamine, 5HT) agonist that binds to all 5HT receptor subtypes, most potently to 5HTIc receptors, with moderate affinity to the 5HTla and 5HT3 receptors. It may have antagonistic effects at the 5HT2 receptor (see Kahn and Wetzler 1991). Although mCPP is primarily used to test the state of the 5HT system, it can also be used to examine interactions between the 5HT and other monoaminergic systems if peripheral markers are available. For instance, a per- ipheral index of central dopamine (DA) activity in response to mCPP challenge could be used to examine the interrelationship between 5HT and DA systems. Measuring plasma concentrations of the DA metabolite, homovanillic acid, in plasma (pHVA) may be an appropriate marker of central DA activity. Although under normal circumstances only 12% of pHVA appears to be of central origin in healthy human subjects (Lambert et al 1991), pharmacological perturbation known to affect brain DA turnover is reflected by parallel changes in pHVA in animal and man. Specifically, administration of apomorphine induces a decrease (probably due to stimulation of presynaptic, inhibitory, DA receptors) in brain and plasma HVA within 30-60 min in rats (Kendler et ai 1982). Conversely, administration of DA antagonists produced an increase (probably due to autoreceptor From the Department of Psychiatry, Mount Sinai School of Medicine, Bronx Veterans Administration Hospital, Bronx, New York. Address correspondenceto Ren6 S. Kahn, MD, Departmentof Psychiatry,Bronx Veterans Administration Hospital, 130 W. Kingsbridge Road, Bronx, NY 10468. Received May 4, 1992; revised August 22, 1992. © 1992 Society of Biological Psychiatry 0006-3223/92/$05.00