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A PET Study After Treatment with an Anxiety-Provoking Agent, m-Chlorophenyl-Piperazine, in Conscious Rhesus Monkeys

Medical and Pharmacological Research Center Foundation, Inoyama-Town, Hakui-City, Ishikawa, Japan

Several PET studies have been performed on conscious nonhuman primates to examine brain function. However, it is unclear how anxiety or stress during PET measurements influences brain function. In the present study, we examined the effects of a well-known anxiety-provoking agent, m-chlorophenyl-piperazine (mCPP), on regional cerebral blood flow (rCBF) and the regional cerebral metabolic rate of glucose (rCMRglc) using PET on conscious rhesus monkeys. Methods: Male rhesus monkeys with experience undergoing PET measurements were used. Twenty and 40 min after mCPP injection (0.2, 1.0, or 5.0 mg/kg intramuscularly; n = 5), rCBF and rCMRglc were measured using an intravenous injection of ¹⁵O-H₂O and ¹⁸F-FDG, respectively. Physiologic parameters, plasma cortisol, and prolactin levels were monitored during PET measurements. Results: Treatment with mCPP significantly increased rCBF in both the cingulate cortex and striatum in a dose-dependent manner, and bell-shaped reductions in rCMRglc were observed for all regions examined. mCPP also significantly increased plasma cortisol and prolactin levels. Physiologic parameters were not affected by mCPP treatment. Conclusion: The present study demonstrates that treatment with the anxiety-provoking agent mCPP significantly affects rCBF and rCMRglc in conscious monkeys. Therefore, since the increases in hormone levels demonstrate that mCPP treatment produced anxiety or stress, these results suggest that anxiety or stress influences conscious brain function. Furthermore, the present study suggests that prevention of anxiety or stress is important when measuring conscious brain function in monkeys.

Key Words: anxiety • nonhuman primates • PET • mCPP