Effect of adrenal and sex hormones on opioid analgesia and opioid receptor regulation

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The role of endocrine factors on opioid analgesia (antinociception) and opioid receptors was studied in male and female Swiss-Webster mice. Morphine was more potent in male than in female mice, although this difference appears to be due to greater availability of morphine to the brain in males. Saturation binding studies indicated that the density and affinity of brain μ- and σ-opioid binding sites were equivalent in males and females. Males and females were implanted SC with naltrexone (NTX) or placebo pellets for 8 days, and then the pellets were removed. This treatment increased the density of μ and σ binding sites in brain and increased the potency of morphine for both sexes, although the increase in antinociceptive effects for males was greater than for females. Adrenalectomy (ADX) in male mice increased the potency of morphine and methadone but did not alter the brain levels of either drug. ADX did not alter brain opioid binding of either μ or σ ligands. When male ADX and control mice were treated with NTX, the potency of morphine and brain opioid binding sites were increased equivalently in both groups. Gonadectomy (GDX) in male mice tended to decrease morphine potency, although this was not found to be a very reliable effect.When male GDX and control mice were implanted with NTX, brain opioid binding was increased similarly in both groups, although morphine potency was increased less in GDX mice. Overall, these studies show that sex differences and hormones of the adrenals and gonads in male mice do not alter brain opioid receptors. Furthermore, these factors do not play a role in NTX-induced opioid receptor upregulation. However, all these factors can modify the potency of opioid agonists.