Age-dependent antinociception and behavioral inhibition by morphine

In current clinical practice, morphine is dosed in older patients based on patient-weight, with different calculations for adjustment. However, at present, neither clinical experience nor the literature offers a clear evidence base for the relationship between antinociception, behavioral effects and morphine administration in older patients. In this study, we compared the nociceptive response of 8 and 24 week old rats after subcutaneous administration of morphine per body weight and analyzed their behavior using an advanced multi-conditioning system. Residual morphine in all major tissues was determined. We observed prolonged morphine-induced antinociception in older rats compared to younger rats. Moreover, morphine significantly stimulated locomotor and rearing behavior 180 min after injection, which was significantly higher in the 8 week compared to 24 week old rats. Tissue analysis from animals extracted 240 min post-injection revealed a significantly higher concentration of residual morphine in the brains of older versus younger animals when standardized on tissue weight. However, this effect was not observed when residual morphine was standardized on protein content. Collectively, our data suggest that in older rats morphine exhibits higher antinociception and increased behavioral inhibition compared to younger animals. This effect is likely due to a significantly higher accumulation of morphine in the brain of older animals.