Influence of gender and castration on liver and CNS N-demethylation of morphine in rats1

Rats were injected with combinations of morphine-N-¹⁴CH₃ and morphine-6³H and the isotope content of the brain and liver was measured by combustion in a tissue oxidizer. The liver of intact male rats showed a significant increase in the ³H to ¹⁴C isotope ratio relative to the blood reflecting the existence of N-demethylation in this organ. This increase was not observed in the liver of either intact females or castrated males or females. Centrally, the hypothalamus, medial thalamus, and corpus striatum of both intact and castrated male and female rats exhibited increases in ³H to ¹⁴C isotope ratios indicating the presence of N-demethylation in these tissues. These results indicate that testicular hormones serve to increase the hepatic N-demethylation of morphine, but apparently reduce the comparable reaction in the CNS.