Naloxone inhibits both glucocorticoid and [D-Ala²,Met⁵]enkephalinamide reversal of behavioural effect of adrenalectomy

Intact rats treated immediately after a 15-min swimming exposure with i.m. 1 or 10 mg/kg naloxone (but not with 10 mg/kg of MRZ2593, a quaternary analogue) showed significant reduction in immobility (55, 30%) compared with controls (70%) during a 5-min retest 24 h later. This effect of naloxone was not seen when administered 1 h prior to retest. Adrenalectomized rats, as previously shown, are only ∼ 30% immobile on retest; administration of [D-Ala², Met⁵]enkephalinamide (50 μg i.m.) or dexamethasone (6 μg i.m.) elecated immobility to 66 and 69% respectively. Administration of naloxone (0.1-10 mg/kg) progressively antagonized the effect of both [D-Ala²,Met⁵]enkephalinamide and dexamethasone, to 36 and 41% immobility on retest at 10 mg/kg. We conclude that the incorporation of information post-stress normally involves at least two opioidergic pathways, and that the integrity of one of these pathways is an absolute requirement for such incorporation to occur, based on the naloxone studies. In contrast, either glucocorticoids or enkephalin analogues are sufficient to restore behaviour post-adrenalectomy, suggesting that corticosteroid-dependent neural mechanisms may substitute for this second opioidergic pathway.