Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats


Baser T., Ozdemir E., Filiz A. K., Taskiran A. Ş., Gursoy S.

CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, vol.99, no.5, pp.461-467, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 99 Issue: 5
  • Publication Date: 2021
  • Doi Number: 10.1139/cjpp-2020-0218
  • Journal Name: CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, CAB Abstracts, Chemical Abstracts Core, EMBASE, Environment Index, MEDLINE, SportDiscus, Veterinary Science Database
  • Page Numbers: pp.461-467
  • Keywords: opioid, ghrelin receptors, hexarelin, GHRP-6, morphine tolerance, SUPRASPINAL LEVEL, NEUROPATHIC PAIN, ANALGESIA, HYPERALGESIA, INVOLVEMENT, EXPRESSION, WITHDRAWAL, MECHANISM, PATHWAY
  • Sivas Cumhuriyet University Affiliated: Yes

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 condusion, these data indicate that administration of GHS-R agonist hexarelin with morphine enhances the antinociception and attenuates morphine tolerance.