Nociceptin/orphanin FQ‐induced delay in gastric emptying: role of central corticotropin‐releasing factor and glucocorticoid receptors

When injected intracerebroventricularly (i.c.v.) in rats, nociceptin/orphanin FQ (N/OFQ) delays gastric emptying and increases plasma corticosterone levels. Our aim in this study was to investigate changes in gastric emptying of a phenol red meal, and the plasma corticosterone response to N/OFQ in adrenalectomized (ADX) rats, in ADX rats injected with corticosterone at 1, 24 and 72 h before the gastric emptying assay, and in intact rats i.c.v. pretreated with a glucocorticoid antagonist (RU486) and with a corticotropin‐releasing factor receptor antagonist (α‐helical CRF9–41). In adrenal intact rats, i.c.v. injection of N/OFQ (2.5 nmol rat−1) significantly delayed gastric emptying (by 70%) and increased plasma corticosterone concentrations. Conversely, in ADX rats, N/OFQ left gastric emptying unchanged. In ADX rats, corticosterone injected at 1, 24 and 72 h before the gastric emptying assay almost restored the N/OFQ‐induced delay in gastric emptying. Finally, pretreatment with RU486‐ and α‐helical CRF9–41 abolished the N/OFQ‐induced inhibition of gastric emptying. These findings suggest that central N/OFQ inhibits gastric emptying through an integrated orphaninergic system–CRF interaction in which corticosterone plays a permissive role.