Hyperresponsivity to the Serotonin Agonist m-Chlorophenylpiperazine in Alzheimer's Disease:  A Controlled Study

• The serotonin agonist m-chlorophenylpiperazine (mCPP) was administered intravenously to 12 patients with Alzheimer's disease and ten age-matched controls. It produced distinct behavioral effects in both treatment groups; however, significantly greater responsivity to mCPP was found in patients with Alzheimer's disease than in controls in measures of psychomotor activation, restlessness, and perceptual abnormalities. Significant and similar increases in plasma prolactin and cortisol levels were found in both patients with Alzheimer's disease and controls following the administration of mCPP vs placebo. Furthermore, blood pressure and pulse changes following mCPP were not significantly different between the groups. Elderly controls, however, did show a significantly greater temperature response following mCPP than did patients with Alzheimer's disease. The overall cognitive effects of mCPP were minimal; however, mCPP produced significantly greater worsening in recent memory and knowledge memory in patients with Alzheimer's disease than in controls. These findings could not be explained by pharmacokinetic differences across populations, because plasma concentrations of mCPP were similar in patients with Alzheimer's disease and controls. The increased behavioral responsivity but unchanged neuroendocrine or other physiologic responsivity to mCPP may be related to damaged brain serotonin neurons or other neuronal systems that interact with serotonin neurons that have been found in postmortem and biopsy studies of patients with Alzheimer's disease.