Adrenalectomy or metyrapone-pretreatment abolishes cerebral metabolic responses to the serotonin agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) in the hippocampus.

1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), a serotonin type 2 (5-HT2) agonist, elevates plasma corticosterone levels and reduces the cerebral metabolic rate for glucose (rCMRglc) in the hippocampus, a structure which possesses few 5-HT2 receptors but a large number of steroid receptors. To explore the hypothetical interaction between 5-HT and steroid mechanisms in the hippocampus, we measured rCMRglc in intact, adrenalectomized and metyrapone-pretreated rats after saline or DOI administration. Metyrapone pretreatment alone had no significant effect on rCMRglc, but adrenalectomy produced widespread rCMRglc increases in the cortex, hippocampus and monoaminergic brainstem nuclei. In intact rats, DOI 10 mg/kg reduced rCMRglc in limbic areas and increased it in the interanteromedial and paracentral thalamic nuclei. Metyrapone pretreatment and adrenalectomy abolished rCMRglc responses to DOI in hippocampal areas and enhanced those in thalamic nuclei. These results indicate that brain responses to DOI are dependent upon the functional state of the hypothalamus-pituitary-adrenal cortex axis.