A PET study following treatment with a pharmacological stressor, FG7142, in conscious rhesus monkeys

Abstract

FG7142 is a benzodiazepine partial inverse agonist, which is known as a pharmacological stressor. Several reports demonstrated that FG7142 produced anxiety in humans, non-human primates, and rodents, and impaired working memory in non-human primates and rodents. In this study, we examined the effect of FG7142 on cerebral blood flow and glucose metabolism using positron emission tomography (PET) in conscious rhesus monkeys. Male rhesus monkeys were intramuscularly treated with FG7142 (0.2 or 1.0 mg/kg, n=5, respectively), and regional cerebral blood flow (rCBF) and regional cerebral metabolic rate of glucose (rCMRglc) were measured by PET 20 min and 40 min after treatment, respectively. During PET measurement, physiological parameters and plasma cortisol levels were monitored. FG7142 significantly decreased rCBF in the thalamus and rCMRglc in all brain regions examined in a dose-dependent manner without changes in physiological parameters. FG7142 also significantly increased plasma cortisol levels. The present study may provide an important insight into the understanding of the pathophysiology of anxiety and stress-related disorders in humans, and strongly suggesting that prevention of anxiety or stress is important when measuring conscious brain function.