NEUROBIOLOGY OF TRYPTOPHAN DEPLETION IN DEPRESSION - EFFECTS OF M-CHLOROPHENYLPIPERAZINE (MCPP)

This study utilized neuroendocrine and mood responses to intravenous ( IV) infusion of the serotonin (5-HT) agonist m-chlorophenylpiperazine (mCPP) to evaluate central 5-HT function in depressed patients undergo ing acute tryptophan (TRP) depletion. Twenty-two drug-free patients wi th DSM-III-R major depression participated. Each patient underwent two randomized, double-blind TRP depletion tests, one sham and one active . At the estimated time of maximum TRP depletion, each patient receive d an IV infusion of mCPP 0.1 mg/kg. Blood was obtained for serum corti sol, prolactin, and growth hormone. Multiple rating scales were used t o assess mood. The cortisol response to IV mCPP was significantly grea ter during TRP depletion than during sham depletion, and free plasma T RP was negatively correlated with the cortisol response during TRP dep letion. These findings are consistent with the hypothesis that acute T RP depletion in drug-free depressed patients induces a compensatory up -regulation of postsynaptic 5-HT receptors, most likely of the 5-HT2A/ 2C subtype. Such changes suggest a mechanism by which acute and potent manipulations of 5-HT function in depressed patients could be used to effect rapid clinical improvement. (C) 1997 American College of Neuro psychopharmacology. Published by Elsevier Science Inc.