Physiologic and neuroendocrine responses to intravenous naloxone in subjects with Alzheimer's disease and age-matched controls

Background: Prior work showed that administration of naloxone HCl had diffe rent behavioral effects in patients with Alzheimer's disease (AD) than cont rols. The aim of the present study was to contrast the physiologic and neur oendocrine responses to administration of a wide range of doses of intraven ous naloxone of patients with probable Alzheimer's disease to aged-matched controls. Methods: This was a double-blind, placebo-controlled, study of 12 patients with probable Alzheimer's disease and 8 age-matched normal controls who eac h received intravenous infusions of naloxone HCl on 3 different days in dos es of 0.1 mg/kg and 2.0 mg/kg preceded by test doses of 0.5 mcg/kg, Order o f treatment condition was randomized. Vital signs and plasma cortisol and p rolactin were obtained at regular intervals. Results: Both groups showed increased cortisol after naloxone 0.1 mg/kg and 2.0 mg/kg (p < .0001), but the increase was significantly greater and long er lived in controls than in patients. Patients, but not controls, also exp erienced a significant hypothermic response after naloxone 2.0 mg/kg (p < . 05). Prolactin, heart rate, and blood pressure did not change following nal oxone and did nor differ between groups. Conclusions: These findings support a growing body evidence that HPA axis a ctivity is increased in AD, and further suggest that at least part of this may be due to decreased opiatergic tonic inhibition. Bioi Psychiatry 1999;4 6:412-419 (C) 1999 Society of Biological Psychiatry.