Effects of single and repeated prolonged stress on mu-opioid receptor mRNA expression in rat gross hypothalamic and midbrain homogenates.

This study tested the hypothesis that stress-induced opioid peptides may have stimulative and inhibitive influence on mu opioid receptor (MOR) mRNA expression and hypothalamus. Several studies have investigated the effects of stress on MOR mRNA expression in rat brain, but almost none compared the response to single versus repeated stresses. Here, we examined the effects of single and repeated stress on MOR mRNA expression in different rat brain regions using reverse transcriptase-polymerase chain reaction (RT-PCR). Following a single episode of restraint stress for 4 h (1R) or 4 h per day on 2 (2R) or 3 (3R) consecutive days, the hypothalamus and midbrain were removed immediately and MOR mRNA levels in both regions were determined by RT-PCR. Blood samples were also collected for simultaneous measurement of serum adrenocorticotropic hormone (ACTH) and corticosterone (CS). MOR mRNA expression was significantly higher in both regions in the 2R group, whereas expression levels in the 3R group did not differ from controls. In the 1R group, hypothalamic MOR expression was equivalent to that in controls, but expression was significantly higher in the midbrain. Serum ACTH levels were significantly higher only in the 1R group, whereas serum CS was significantly higher in both the 1R and 3R groups. Our findings indicate that the influence of restraint stress on MOR mRNA expression in the hypothalamus is different than in the midbrain region in rats. Endogenous opioid peptides released in response to stress may paradoxically have an effect on the HPA axis.