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 different behavioral effects in patients with Alzheimer’s disease (AD) than controls. The aim of the present study was to contrast the physiologic and neuroendocrine responses to administration of a wide range of doses of intravenous 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 each received intravenous infusions of naloxone HCl on 3 different days in doses of 0.1 mg/kg and 2.0 mg/kg preceded by test doses of 0.5 mcg/kg. Order of treatment condition was randomized. Vital signs and plasma cortisol and prolactin 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 longer lived in controls than in patients. Patients, but not controls, also experienced a significant hypothermic response after naloxone 2.0 mg/kg (p< .05). Prolactin, heart rate, and blood pressure did not change following naloxone and did not differ between groups. Conclusions: These findings support a growing body evidence that HPA axis activity is increased in AD, and further suggest that at least part of this may be due to decreased opiatergic tonic inhibition.