Brain research
-
Comparative Study
Comparison of the antinociceptive effect of acute morphine in female and male Sprague-Dawley rats using the long-lasting mu-antagonist methocinnamox.
Male rats are more sensitive than female rats to the antinociceptive action of morphine. The present study used age-matched (9-10 weeks old) male and female Sprague-Dawley rats to investigate whether this difference is due to variation in micro-opioid receptor binding and G protein activation. In the warm-water tail-withdrawal assay at both 50 degrees C and 55 degrees C, morphine was 2-3 times more potent in males than females. ⋯ Pretreatment of male rats with 0.32 mg/kg methocinnamox reduced the antinociceptive potency of morphine to that observed in female rats expressing a full complement of micro-opioid receptors. However, with increasing pretreatment doses of methocinnamox, the maximal antinociceptive effect of morphine was decreased in females but not males. The results suggest that pathways downstream of the micro-opioid receptor and G protein are more efficient in male rats than in female rats such that there is a larger receptor reserve for morphine-mediated antinociception.
-
Perinatal hypoxia-ischemia (HI) is associated with delayed cerebral damage, which involves receptor-mediated excitotoxicity. Until now, successful interventions to reduce excitotoxicity early after HI in experimental settings failed to transform into clinical applications owing to negative side effects. A promising new approach using the anticonvulsant Topiramate (TPM) has shown to be effective to reduce brain damage after early HI in a rodent model of combined TPM-hypothermia. Here, we used TPM solely administered 1 h after HI in a neonatal piglet model in order to verify possible neuroprotection. ⋯ Exclusive TPM treatment shows neuroprotection in newborn piglets after HI.