Seven days after removal of the adrenals in rats, the messenger RNA levels of preproenkephalin (ENK), preprodynorphin (DYN), cholecystokinin (CCK), and neuropeptide Y (NPY) were measured in hippocampus, striatum, and hypothalamus. Adrenalectomy (ADX) in the morning, when endogenous corticosterone levels were low, resulted 7 days later in a decrease of ENK mRNA and DYN mRNA levels in the hippocampus (41.3 +/- 4.3 and 41.9 +/- 5.7%, respectively) and in the striatum (32.1 +/- 6.6 and 31.2 +/- 12.9%, respectively), but no change was observed in the ENK mRNA content of the hypothalamus. When ADX was performed in the evening the opioid mRNA levels were not changed in these brain areas 7 days after ADX. Pretreatment with a single dose of corticosterone before surgery in the morning produced high corticosterone levels similar to those in the evening and prevented the decrease of ENK mRNA in the hippocampus. The decrease in hippocampal DYN mRNA and in striatal ENK mRNA and DYN mRNA persisted. CCK mRNA and NPY mRNA were not changed in any of the experimental groups in any of the three examined brain areas. This study demonstrates that ADX decreases opioid gene expression in the rat hippocampus and striatum. The effect of ADX on hippocampal ENK mRNA levels that persists for at least 7 days postsurgery is independent of the circulating corticosterone level at the time of surgery.