ABSTRACT
m-Chlorophenylpiperazine (mCPP) is a metabolite of the antidepressant trazodone which has been widely used in psychopharmacology research as a probe of serotonin (5-hydroxytryptamine; 5-HT) function. However, in addition to binding at 5-HT receptors it also binds strongly to alpha 2-adrenoceptors, and it is conceivable that some of the physical and psychological symptoms previously reported following mCPP infusion are due to effects upon central noradrenergic neurotransmitter function. In this double-blind placebo-controlled balanced-crossover study in 12 healthy male volunteers we have examined the effects of infusion of mCPP (0.08 mg/kg over 2 min) on symptoms of anxiety, cognitive performance, pulse and blood pressure, and plasma concentrations of adrenocorticotrophic hormone (ACTH), cortisol, prolactin, growth hormone, and the noradrenaline metabolite 3-methoxy-4-hydroxyphenyl glycerol (MHPG). The results confirm previous findings that in humans mCPP causes significant increases in the symptoms of anxiety, and in the plasma concentrations of cortisol, prolactin and growth hormone. In addition, our results demonstrate that mCPP causes no significant changes in cognitive performance, in pulse or systolic blood pressure, or in the plasma concentration of MHPG. Since pulse, systolic blood pressure and MHPG plasma concentrations all to some degree reflect central noradrenergic activity, we believe it unlikely that the psychological and hormonal effects of mCPP are due primarily to effects on noradrenergic neurotransmission. Further studies to address this specific issue are needed, however, before firm conclusions can be reached.
