Morphine inhibition of plasma corticosteroid levels in chronic venous-catheterized rats

Abstract

Unanesthetized rats with chronic venous catheters show a diurnal increase in plasma corticosteroid levels at 5 pm over those noted at 9 and 10 am and 3 pm. At 10 am, 1 hour after the injection of morphine via the catheter, a 390% increase in plasma corticosteroid levels was noted. Eight hours after injection of morphine these levels were depressed 51% when compared with saline-injected controls. Results indicate morphine initially elicits a hypersecretion of ACTH by direct activation of the pituitary-adrenal axis and not via sensory stimulation accompanying the stress of intravenous injection of the drug. A secondary effect of morphine, inhibitory in action, appears exerted on neurogenic factors regulating diurnal variation in plasma corticosteroid levels.

Differences in Hypothalamo-Pituitary-Adrenocortical Activity in the Rat after Acute and Prolonged Treatment with Morphine

“…The ability of morphine to stimulate the release of ACTH in the rat and several other species is well known [3,9,18,19,20,26,28,33]. This response is probably not due to non-spe cific stressful effects of the drug for, if it were, the adrenocorticotrophic response to a subsequent stress would be normal [15] or attenuated [30] and not potentiated as our data and those from earlier studies, in which adrenaline [9] or ether [20,21] were employed as stressors, illustrate.…”

“…Neither the density nor the affinity of 3H-naloxone binding sites in the hypothalamus was influenced by the morphine treatment. The results suggest the opioid peptides and their receptors play a major role in the regulation of HPA function.The functional activity of the hypothalamo-pituitaryadrenocortical (HPA) axis in the rat [5,9,18,19,26,33] and other species [3,20] may be influenced profoundly by opiate drugs. Many years ago Briggs and Munson [5] showed in the rat that a single injection of morphine causes a marked depletion of adrenal ascorbic acid but that prolonged treat ment with the opiate inhibits the adrenocortical response to stress.…”

Site of Action of Vasopressin in Causing Corticotropin Release1

“…It is similarly effective in man (35,36) even without pentobarbital. In other species, and in some cases in the rat, it has been reported to fail to prevent ACTH release (37)(38)(39). In the present experiments, morphine was used in combination with pentobarbital and dexamethasone, and was effective in diminishing ACTH release following all doses of vasopressin used centrally or intravenously.…”

The Effect of Carbon Tetrachloride on Plasma Corticosterone Level

“…The hypophyseo-adrenal function has diurnal variation and is very susceptible to external stimuli such as the emotional stress of a strange environment. So the corticoid level elevates progressively in day time though it is rather lower in the morning (8). It likewise rises when the animals are moved from the animal quarter to the laboratory.…”