Effects of naloxone on plasma corticosterone in the opiate-naive rat

Naloxone HCl (NX) has long been considered to be a pure narcotic antagonist, having an effect only subsequent to pretreatment with a narcotic. Characteristically, low doses of NX have been used to antagonize the effects of analgesic doses of narcotics and to precipitate withdrawal in chronically treated animals. In this study, the effects of high doses of NX (2.0–20.0 mg/kg) on changes in plasma corticosterone were examined in the opiate-naive animal. Using male rats with chronic intravenous catheters and one-way vision boxes, injections were made and serial blood samples were obtained in the conscious, unrestrained animal. The acute administration of NX to the opiate-naive animal produced a dose-related increase in plasma corticosterone with respect to both amplitude and duration. NX (10.0 mg/kg i.v.) produced a significant elevation in hormone level at 15 and 30 minutes. With NX (20.0 mg/kg i.v.) the duration of the response was extended to 60 minutes. To examine whether short-term tolerance to this effect could be produced, animals were given a single pretreatment with either NX (10.0 mg/kg) or saline i.v. Two hours later NX produced a similar elevation in hormone level in both groups. The effect of chronic injection of NX was also studied. Animals pretreated with either NX (10.0 mg/kg) or saline s.c. once daily for 7 days did not show a significant difference following the subsequent administration of NX. In both cases, a significant elevation of plasma corticosterone resulted. The results suggest that NX may have a direct effect on opiate receptors resulting in an elevation of plasma hormone levels or NX may be disrupting an endogenous opiate-receptor interaction producing a stress response.     

Effects of stress on immune responsiveness, gastric ulcerogenesis and plasma corticosterone in rats: modulation by diazepam and naltrexone

Effects of restraint stress (24 hr at room temperature) were evaluated on some immunological, visceral and endocrinal responses in rats. In animals sensitized with sheep RBC (SRBC), restraint stress (a) prevented the booster-induced rise in anti-SRBC antibody titre, (b) induced gastric mucosal erosions, and (c) elevated plasma corticosterone, when compared to non-stressed controls. Diazepam (1 or 10 mg/kg) consistently attenuated the effects of stress on all three parameters studied. The opioid antagonist, naltrexone (1 or 5 mg/kg) tended to aggravate these stress-induced effects. These concurrent biological changes during stress and their modulation by drugs are discussed in light of a possible correlation between endocrinal, immunological and visceral changes during such aversive stimuli.     

Effects of naltrexone on lipopolysaccharide-induced sepsis in rats

Naltrexone, an opioid antagonist, has been reported to possess an anti-inflammatory effect via blockade of opioid receptor. The aim of this study is to evaluate the protective effect of naltrexone on LPS-induced septic shock in rats. Sepsis was induced by administration of LPS (10 mg/kg, i.v.) in anesthetized rats. Results demonstrated that pretreatment with naltrexone (10 mg/kg, i.v.) significantly ameliorated hypotension and bradycardia of rats 6 h after LPS administration. In isolated blood vessel, study showed that pretreatment with naltrexone significantly improved norepinephrine-induced vasoconstriction and ACh-induced vasorelaxation in aorta of endotoxemic animals. Naltrexone significantly reduced the elevation of serum glutamate-oxalacetate transaminase and glutamate-pyruvate transaminase (as index of hepatic function) induced by LPS. The infiltration of polymorphonuclear neutrophils into liver 48 h after LPS treatment in mice was also reduced by naltrexone. On the other hand, naltrexone significantly decreased the levels of plasma TNF- and inhibited overproduction of superoxide anions in aortic rings. However, naltrexone did not suppress the overproduction of NO (measured by its metabolites nitrite/nitrate in plasma) and iNOS expression in lungs induced by LPS. In in vitro study, naltrexone did not attenuate non-enzymatic iron-induced lipid peroxidation in rat brain homogenates. In conclusion, pretreatment with naltrexone significantly improved circulatory failure and hepatic dysfunction in sepsis. These effects were associated with reduction of TNF- levels and superoxide anion formation, which may be attributed to antagonism of opioid receptors.     

Effects of intrahippocampal injection of chemicals on the levels of plasma corticosterone in rats.

The possibility that the hippocampus can influence the function of the hypothalamo-pituitary-adrenal axis was examined by injecting small quantities of various neurotransmitter substances into this brain structure. Injections of either noradrenaline or 5-hydroxytryptamine into the dorsal hippocampus had no effect on plasma concentrations of corticosterone (B). An injection of carbachol into the dorsal hippocampus elicited a significant rise in B concentrations, while that of hemicholinium into the same brain structure resulted in an inhibition of noise-induced rise of plasma B concentration. An injection of carbachol into the dorsal hippocampus counteracted dexamethsone-induced decrease in plasma B concentration, while that of hemicholinium enhanced it.     

Effects of S-petasin on corticosterone release in rats

Petasites hybridus is used in Chinese herbal medicine. S-petasin is a bioactive compound isolated from leaves or roots of Petasites hybridus. S-petasin has been used to relieve gastrointestinal pain, lung disease, and spasms of the urogenital tract. However, the side effect of S-petasin on endocrine systems are still not clear. This study explored the effects of S-petasin on the release of corticosterone in vivo and in vitro. An intravenous injection of S-petasin (10 microg/kg) decreased both basal and adrenocorticotropin (ACTH)-induced plasma corticosterone concentration in male rats. In vitro, S-petasin (3 x 10(-6) - 10(-4) M) caused a significant reduction of basal and ACTH-stimulated release of corticosterone from the enzymatically dispersed rat zona fasciculata-reticularis (ZFR) cells in a dose-dependent manner. In order to study possible mechanisms, ZFR cells were incubated with S-petasin (10(-5) M) in the presence or absence of forskolin (adenylate cyclase activator, 10(-6) - 10(-4) M), 8-Br-cAMP (a cAMP analogue, 10(-6) 10(-4) M), 25-OH-cholesterol (pregnenolone biosynthesis precursor, 10(-5) M) combined with trilostane (a blocker of 3beta-hydroxysteriod dehydrogenase, 3beta-HSD, 10(-6) M) and deoxycorticosterone (corticosterone biosynthesis precursor, 10(-9) - 10(-6) M) at 37 degrees C for 1h. The concentration of pregnenolone and corticosterone in media were measured by radioimmunoassay. The stimulatory effects of corticosterone secretion induced by forskolin (10(-5) - 10(-4) M), 8-Br-cAMP (10(-5) - 10(-4) M) and deoxycorticosterone (10(-7) - 10(-6) M) were reduced by S-petasin at 10(-5) M. The stimulatory effects of pregnenolone secretion induced by 25-OH-cholesterol combined with or without trilostane was reduced by S-petasin at 10(-5) M. These results suggest that S-petasin inhibits the production of corticosterone from rat ZFR cells in part through decreasing the activities of adenylyl cyclase, P450scc and 11beta-hydroxylase.     

Effects of estradiol on corticosterone secretion in ovariectomized rats

The effects of estradiol benzoate (EB) on steroidogenesis in rat zona fasciculata-reticularis (ZFR) cells were studied. Female rats were ovariectomized (Ovx) for 2 weeks and then injected subcutaneously with oil or EB for 3 days before decapitation. ZFR cells were isolated and incubated with adrenocorticotropin (ACTH) or prolactin (PRL) for 1 h. Corticosterone concentrations in plasma and cell media, and adenosine 3',5'-cyclic monophosphate (cAMP) production in ZFR cells were determined by radioimmunoassay. The effects of EB replacement in vivo on the activities of steroidogenic enzymes in ZFR cells were measured by the amounts of intermediate steroidal products separated by thin-layer chromatography. Replacement of EB in vivo resulted in a dose-dependent increase of plasma PRL and corticosterone in Ovx rats. The basal, ACTH-, and PRL-stimulated release of corticosterone by ZFR cells was greater in EB- than in oil-treated animals. Forskolin-induced production of cAMP was greater in the EB-replaced rats than in oil-treated animals, which correlated with the increase of corticosterone production. The 3-isobutyl-l-methylxanthine (IBMX) plus ACTH-, IBMX plus PRL-, and forskolin plus PRL-stimulated productions of cAMP were higher in EB- than in oil-treated rats. The enzyme activities of postpregnenolone were not affected by EB replacement in Ovx rats. These results suggest that the EB-related increase of corticosterone production in Ovx rats is associated with an increase of cAMP generation and the stimulatory effect of PRL on ZFR cells.     

Dose-related dual action of corticosterone on hypothalamic serotonin content in rats.

The effect of corticosterone administered in different doses has been studied on hypothalamic serotonin (5-HT) content. A single intraperitoneal injection of the hormone in doses of 1.0 and 2.0 mg/kg bw. increased the serotonin content of the hypothalamus at 30 min after administration. Five mg/kg had no effect, while 10.0 mg/kg decreased the serotonin content. The data provide an explanation for the controversial findings of different authors having used different doses of different glucocorticoids and on the basis of the results it is emphasized that the action of glucocorticoids on hypothalamic 5-HT content is a dose-dependent dual effect.     

Effects of metyrapone on plasma corticosterone concentration in Gallus domesticus

l. Metyrapone (75 or 150 mg/kg body wt) was injected into fed and starving birds and their plasma corticosterone concentrations monitored.2. Metyrapone stimulated a hypercorticosteronaemia in fed but not in starving birds. It persisted for up to 4 hr. No significant hypocorticosteronaemia was noted subsequently.3. Pretreatment (2 hr) with metyrapone inhibited the response to exogenous ACTH.     

Factors modifying the effect of diazepam on plasma corticosterone levels in rats

We have examined factors that alter the effect of diazepam (DZ) on plasma corticosterone (CS) in rats. DZ had a biphasic effect on plasma CS levels: CS decreased with doses below 5 mg/kg and increased with higher doses. Peak response occurred 90 minutes post injection in both sexes. Plasma DZ levels were significantly higher in females than in males and peak at 10 and 30 minutes post injection in males and females, respectively. There was also a sex difference in the pattern of DZ metabolites. An acute stressor (30 minutes of immobilization) did not affect plasma CS levels in rats injected with a 5 mg/kg dose of DZ. Prenatally stressed animals did not differ in basal CS levels or in their response to 5 mg/kg of DZ compared to prenatally non-stressed animals. These two groups of animals also did not differ in plasma levels of DZ or of its metabolites. By contrast, the 5 mg/kg dose of DZ had no effect on plasma testosterone levels in control animals, but increased it in prenatally stressed animals. Furthermore, compared to non-stressed controls, prenatally stressed animals had lower baseline plasma testosterone levels. These results indicate that the effect of DZ on plasma CS is influenced by endogenous as well as exogenous factors and that these effects vary with the particular biochemical parameter under examination.     

A radioimmunoassay for plasma corticosterone

A radioimmunoassay for plasma corticosterone has been developed. Antiserum against corticosterone was produced in rabbits immunized with corticosterone -21- hemisuccinate conjugated to bovine serum albumin. The assay was practical and reliable. The coefficient of variation between assays was ± 23% and among assays was ± 8%. Plasma corticosterone of mice is measured readily by assaying directly aliquots of a methylene chloride extract of 40 μl of plasma. The mean plasma corticosterone concentration of mice was similar to that obtained by other methods.     

Effects of anterior pituitary hormones on hepatic corticosterone metabolism in rats

Experiments were conducted to determine the effects of anterior pituitary hormones on hepatic corticosterone metabolism in rats. Hypophysectomy lowered A-ring reduction but did not affect sidechain metabolism. Administration of prolactin, FSH, LH or FSH + LH to hypophysectomized rats affected neither process. Similarly, ACTH or growth hormone, when given alone, did not affect corticosterone metabolism. However, combined treatment with ACTH and growth hormone significantly reduced the rate of ring A metabolism, suggesting that hormonal interactions may be important in the control of hepatic steroid metabolism.     

The effect of sex on central histaminergic responses and corticosterone bioperiodicity in Sprague-Dawley rats

Male and female rats demonstrate a difference in the relationship between food intake and H(1) receptor binding, which may be due to hormonal differences that exist. The relationship between the endocrine and histaminergic regulation and synchronization of food intake needs to be elucidated. Male and female rats fed 25% protein displayed bioperiodicity in mean corticosterone levels of 148.95+/-33.71 and 288.48+/-47.84 ng/ml, respectively. Accompanying bioperiodic times were of 22.43+/-1.35 h (males) and a period of 21.42+/-1.96 h (females). Central H(1) receptors in male rats had a mean bioperiodic value of 102.37+/-1.95 pmol/g protein with a period of 21.66+/-1.85 h, while that for females was 97.42+/-4.19 pmol/g protein with a period of 10.23+/-0.95 h. Central histaminergic activity affects feeding in rats with distinct gender variation that is bioperiodic in nature and functions as a major regulatory mechanism.     

Activation of CCK-A receptors induces elevation of plasma corticosterone in rats.

Cholecystokinin octapeptide (CCK-8) and ceruletide (1 microgram/kg) produced a pronounced increment of plasma corticosterone levels at 30 min after intraperitoneal administration. The response to these peptides was suppressed by pretreatment with a selective antagonist for CCK-A receptors, (-)L-364,718, in a dose-related manner, but not with an antagonist for CCK-B receptors, (+)L-365,260. However, (-)L-364,718 itself had no effect on basal levels of plasma corticosterone. These results indicate that peripheral administration of CCK-8 and ceruletide stimulates the hypothalamo-pituitary adrenal axis through the activation of CCK-A receptors, but not CCK-B receptors.