Study summary · research use only
Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this rat study using 104 Wistar albino male rats weighing approximately 220-240 g, the effects of the ghrelin receptor agonist hexarelin (0.2 mg/kg) and antagonist [d-Lys3]-GHRP-6 (10 mg/kg) on morphine (5 mg/kg) antinociception and tolerance were evaluated using a three-day cumulative dosing regimen and tail-flick and hot-plate tests at 30-min intervals (0, 30, 60, 90, and 120 min). The abstract reports that hexarelin combined with morphine attenuated analgesic tolerance to morphine and increased the analgesic effect, while [d-Lys3]-GHRP-6 showed no significant analgesic activity on its own. The authors describe hexarelin as enhancing antinociception and attenuating morphine tolerance when co-administered with morphine.
Abstract
Ghrelin, a peptide hormone released from the gastric endocrine glands, shows analgesic activity apart from its various physiological effects. Nevertheless, the effects of ghrelin receptor (GHS-R) agonists on morphine analgesia and tolerance have not yet been elucidated. The purpose of this study was to evaluate the effects of the ghrelin receptor agonist hexarelin and antagonist [d-Lys3]-GHRP-6 on morphine antinociception and tolerance in rats. A total of 104 Wistar albino male adult rats (weighing approximately 220-240 g) were used in the experiments. To induce morphine tolerance, a three-day cumulative dose regimen was used in the rats. Then, randomly selected rats were evaluated for morphine tolerance on day 4. The analgesic effects of hexarelin (0.2 mg·kg-1), [d-Lys3]-GHRP-6 (10 mg·kg-1), and morphine (5 mg·kg-1) were measured at 30-min intervals (0, 30, 60, 90, and 120 min) by tail-flick and hot-plate analgesia tests. The findings suggest that hexarelin in combination with morphine attenuates analgesic tolerance to morphine. On the other hand, ghrelin receptor antagonist [d-Lys3]-GHRP-6 has no significant analgesic activity on the morphine tolerance in analgesia tests. Furthermore, co-administration of hexarelin and morphine increases the analgesic effect. In conclusion, these data indicate that administration of GHS-R agonist hexarelin with morphine enhances the antinociception and attenuates morphine tolerance.
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