Effect of ACTH-like peptides on morphine-induced hypothermia in unrestrained guinea pigs

Peripheral treatment with adrenocorticotropin (1–24) (ACTH 1–24), at different doses and sequences, consistently antagonized the decrease in body temperature produced by morphine in the freely moving guinea pig, whereas adrenocorticotropin (4–10) (ACTH 4–10), which lacks corticotrophic activity, was partially effective only when it was administered in a high dose 24 h prior to morphine. Centrally administered ACTH 1–24 completely prevented the hypothermic effect of intracerebroventricularly (i.c.v.)-injected morphine. Likewise, the i.c.v. administration of ACTH 4–10 was equally effective in blocking the i.c.v. morphine-induced hypothermia. Neither ACTH 1–24 nor ACTH 4–10 did produce changes in body temperature. These results suggest that peripherally administered ACTH 1–24 antagonizes indirectly the actions of morphine through the release of adrenal corticosteroids, whereas centrally injected ACTH 1–24 or ACTH 4–10 act as direct antagonists of morphine effects through opioid receptors.