Rise In Plasma Corticosterone Concentration Research Articles

Sex differences in cardiovascular, neuroendocrine and behavioral changes evoked by chronic stressors in rats

This study investigated the physiological, somatic and behavioral changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in male and female rats. For this, adult Wistar rats were subjected to a 10days regimen of repeated restraint stress (RRS, homotypic stressor) or chronic variable stress (CVS, heterotypic stressor). Effects evoked by CVS included: (i) adrenal hypertrophy and decreased body weight gain in male animals, (ii) a sympathetically-mediated increase in basal heart rate in males, and (iii) a rise in plasma corticosterone concentration and anxiogenic effects in female animals. The homotypic stressor RRS also induced an increase in plasma corticosterone and anxiogenic effects in females, decreased body weight gain in males and evoked a sympathetically-mediated increase in heart rate in both sexes. Changes in cardiovascular function and autonomic activity evoked by both stressors were followed by impairment of baroreflex activity in males, but not female animals. Both chronic stressors evoked changes in blood pressure responsiveness to vasoconstrictor and vasodilator agents in both sexes. Taken together, these results indicate that regardless of chronic stress regimen males are more vulnerable to somatic effects of chronic stressors, while females appear to be more susceptible to neuroendocrine and behavioral changes. Present findings also indicate that females are selectively vulnerable to cardiovascular and autonomic changes evoked by homotypic stressors. Nevertheless, homotypic and heterotypic stressors similarly affect cardiovascular function and autonomic activity in males.

Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment

Organophosphates are cholinesterase (ChE) inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours) rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP) poisoning symptomatology. In rodents, corticosterone (CORT) is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentration (the CORT response) and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET) [2-methyl-1,2-di(pyridin-3-yl)propan-1-one] blocks CORT synthesis by inhibiting steroid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP) [2-chloro-1-(2,4-dichlorophenyl) ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. The purpose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. The following was observed in the MET-treated rats: i) no rise in plasma CORT concentration after the CVP administration, ii) a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.

Corticosterone alone does not trigger a short term behavioural shift in incubating female common eiders Somateria mollissima, but does modify long term reproductive success

The trade‐off between reproductive effort and adult survival in birds is modulated by several factors. Corticosterone and prolactin have additive effects on reproductive behaviour by stimulating foraging and parental behaviours, respectively. When incubation is associated with fasting, nest desertion is supposed to be activated by an unknown refeeding signal when body condition becomes critically deteriorated. The concomitant rise in corticosterone levels has been suggested to be the triggering factor. We tested the role of corticosterone on reproductive success by observing the effect of corticosterone implants on reproductive success and on plasma prolactin concentration in female common eiders Somateria mollissima. Implanted females showed a significant increase in corticosterone and a decrease in prolactin levels. Despite their enhanced daily body mass loss, females did not abandon incubation nor did they start to refeed in the four days following implantation. These data show that the experimentally induced rise in plasma corticosterone concentration alone does not trigger nest desertion. However, after 25 days of incubation, implanted females displayed a higher rate of egg loss, suggesting lower nest attentiveness towards the end of incubation. We suggest that the short‐term effects of corticosterone may be dependent on the energy state of the bird. However, the late‐induced change in reproductive success is indirectly linked to corticosterone, and we suggest that either a prolactin decrease, or a depletion in protein body reserves, may participate in the long‐term adjustment of incubation behaviour in female eiders.

Enhanced 5-HT1A receptor expression in forebrain regions of aggressive house mice

The brain 5-HT 1A receptor system in male wild house mice selected for high and low offensive aggression was investigated by autoradiographic analysis of in situ hybridization and radioligand binding. In high-aggressive mice, characterized by a short attack latency, the rise in plasma corticosterone concentration during the early dark phase was reduced. At that time the level of 5-HT 1A mRNA in the dorsal hippocampus (dentate gyrus and CAI) was twice the amount measured in low-aggressive mice that had long attack latency and high plasma corticosterone level. Increased postsynaptic 5-HT 1A receptor radioligand binding was found in dentate gyrus, CA1, lateral septum, and frontal cortex. No difference in ligand binding was found for the 5-HT 1A autoreceptor on cell bodies in the dorsal raphe nucleus. In conclusion, genetic selection for high offensive aggression co-selects for reduced (circadian peak) level in plasma corticosterone and increased postsynaptic 5-HT 1A receptor number in limbic and cortical regions.

Enhanced 5-HT 1A receptor expression in forebrain regions of aggressive house mice

The brain 5-HT 1A receptor system in male wild house mice selected for high and low offensive aggression was investigated by autoradiographic analysis of in situ hybridization and radioligand binding. In high-aggressive mice, characterized by a short attack latency, the rise in plasma corticosterone concentration during the early dark phase was reduced. At that time the level of 5-HT 1A mRNA in the dorsal hippocampus (dentate gyrus and CAI) was twice the amount measured in low-aggressive mice that had long attack latency and high plasma corticosterone level. Increased postsynaptic 5-HT 1A receptor radioligand binding was found in dentate gyrus, CA1, lateral septum, and frontal cortex. No difference in ligand binding was found for the 5-HT 1A autoreceptor on cell bodies in the dorsal raphe nucleus. In conclusion, genetic selection for high offensive aggression co-selects for reduced (circadian peak) level in plasma corticosterone and increased postsynaptic 5-HT 1A receptor number in limbic and cortical regions.

Release of corticosterone from the rat adrenal cortex in response to administration of (1-24)adrenocorticotrophin.

The intraperitoneal injection of (1-24)ACTH (34-170 nmol/kg) in rats pretreated with betamethasone resulted in a biphasic rise in plasma corticosterone; only a single phase-response was observed after lower doses (3.4-17.0 nmol/kg). There was an initial rapid rise to a level of approximately 0.72 mumol corticosterone/l plasma over the first 10 min after injection, followed by a plateau phase in which there was no further significant rise in steroid levels up to 25 min. Between 25 and 30 min after injection there was a second significant rise in plasma corticosterone concentration. The amplitude of the first phase of steroid increase was essentially the same for all doses of (1-24)ACTH administered whereas the amplitude of the second phase was dose-dependent. The administration of the microtubule inhibitor, colchicine, greatly reduced the amplitude of the second phase of the response to (1-24)ACTH while not affecting the first phase. However, a second stimulus with (1-24)ACTH in colchicine-treated animals was without effect on plasma corticosterone concentrations; both the first and second phases of corticosteroid increase being abolished. It is proposed that the first phase of plasma corticosterone increase resulted from the release of corticosteroid from a storage form close to the cell membrane and not requiring microtubular transport, whereas the second phase was the result of transport from more distant storage sites or de-novo synthesis.

Effect of diazepam on stress induced changes in brain histamine

Acute treatment with diazepam (2.5, 5 and 10 mg/kg) did not affect the basal histamine concentration in the hypothalamus, midbrain or in the cortex of the rat. The increase in the hypothalamic histamine level caused by 15 min of “platform stress” was significantly attenuated by diazepam (5 or 10 mg/kg) pretreatment, but the elevation induced by 15 min of air blasts remained unchanged. Diazepam significantly reduced the rise in plasma corticosterone concentration in response to air blast stress but did not affect the increase caused by “platform stress.” Thus, in addition to the already known effects of diazepam on stress induced changes in other central neurotransmitters or neuromodulators, diazepam may also affect the hypothalamic histamine elevation induced by certain type of stress.

Rise of plasma corticosterone concentrations in rats immediately before and after birth and in fetal rats after the ligation of maternal uterine blood vessels or of the umbilical cord.

Just before normal vaginal delivery the plasma corticosterone concentration (PCC) in fetal rats increased markedly compared with that on day 22 of gestation. The PCC was elevated 2 h after birth and then declined until 12 h after birth, when it approached the level found on day 22 of gestation. Similarly, in premature newborn rats obtained by cesarean delivery on days 21 and 22 of gestation, the PCC increased 2 to 4 h after delivery and then declined. The PCC in 22-day-old fetal rats, 30 min after ligation of the maternal blood vessels running along a uterine horn, rose markedly compared with that in fetuses in the contralateral intact horn. A similar increase in PCC was not observed in either decapitated or encephalectomized fetuses, but observed in fetuses whose umbilical cords were ligated. The rise in fetal PCC after ligation of uterine blood vessels and of umbilical cords was considerably higher than that observed after various stresses reported by other investigators and also higher than that found 60 min after maternal adrenalectomy. The rise in PCC just before and just after birth and after the ligation should not be considered as the result of stress, parturition or ligation, but may be a result of the response to other factors.

Effects of Δ9 - THC on growth hormone and ACTH secretion in rats

Δ 9 - THC in doses of 5 – 20 mg/kg caused inhibition of GH secretion and stimulation of ACTH secretion. A rise in plasma corticosterone concentration following injection of Δ 9 - THC was used as an index of increased ACTH secretion. Daily administration of 20 mg/kg of Δ 9 - THC for 20 days did not result in significant tolerance to its neuroendocrine effects. Dexamethasone blocked the acute stimulant ffect of Δ 9 - THC on ACTH secretion but did not alter its inhibitory effects on GH secretion. Pentobarbital also suppressed pituitary-adrenal activation by Δ 9 - THC but was less effective than dexamethasone; the pentobarbital-induced rise of plasma GH, however, was suppressed by Δ 9 - THC. These results show that Δ 9 - THC acts as a pharmacological stressor of hypothalamo-pituitary function in rats since the same changes in plasma corticosterone and GH concentrations are elicited in response to many stimuli that are commonly of a stressful nature.

Tolerance to the effect of delta1-tetrahydrocannabinol on corticosterone levels in mouse plasma produced by repeated administration of cannabis extract or delta1-tetrahydrocannabinol.

1 Three injections of cannabis extract (500 mg/kg s.c. given over 3 or 5 days) diminished thymus gland weight but not the weights of spleen or liver in weanling female and adult male mice kept at room temperature.2 Both cannabis extract (500 mg/kg s.c.) and Delta(1)-tetrahydrocannabinol (Delta(1)-THC; 10 and 20 mg/kg i.p.) elevated corticosterone levels in mouse plasma.3 A pretreatment that consisted of three daily subcutaneous injections of 500 mg/kg of cannabis extract and that was shown to produce tolerance to the ;cataleptic' effect of Delta(1)-THC (2 mg/kg i.v.) in mice, also produced tolerance to the effect of Delta(1)-THC (10 mg/kg i.p.) on corticosterone levels in mouse plasma. However, this pretreatment did not reduce the rise in plasma corticosterone concentration produced by immobilization.4 Tolerance to the effect of Delta(1)-THC (10 mg/kg i.p.) on corticosterone levels in mouse plasma was also produced by the pretreatment of mice with a single injection of Delta(1)-THC (10 mg/kg s.c.). Three daily injections of Delta(1)-THC (10 or 30 mg/kg s.c.) also produced tolerance.5 In a thermoneutral environment (30-32 degrees C) in which cannabis extract does not produce hypothermia, the drug no longer reduced thymus gland weight. However the effect of cannabis extract and of Delta(1)-THC on corticosterone plasma levels was the same at room temperature as at 30-32 degrees C. Tolerance to the latter effect of Delta(1)-THC was also produced equally readily under the two conditions.6 It is concluded that pretreatment with cannabis extract or Delta(1)-THC can produce tolerance to the effect of Delta(1)-THC on corticosterone levels in mouse plasma and does so without impairing the effect of immobilization stress on corticosterone release. In addition, both the rise in corticosterone plasma levels produced by cannabis or Delta(1)-THC and the development of tolerance to this effect can still take place in the absence of hypothermia.

Spinal cord pathways involved in tourniquet stimulation of ACTH secretion.

The effect of complete transection or hemisection at various levels from the lumbar through the cervical spinal cord on a stress-induced change in plasma corticosterone concentration was studied in adult male pentobarbital-anesthetized rats. Stressors were a hind-leg tourniquet 1–5 days and a hind-leg break 5 or 10 days postoperatively. A rise in plasma corticosterone concentration 20 min after the onset of the stress was generally used as an index of ACTH secretion. Neither stressor stimulated ACTH secretion in rats with complete cord transection between L1 and T2. Hemisection between L1 and T10 did not consistently block ACTH secretion following ipsilateral or contralateral tourniquet or leg break, but hemisection above T10 blocked the effect of only the contralateral stressors. Complete cord transection above T2 was associated with elevated ‘basal’ plasma immunoreactive ACTH and corticosterone concentrations in unanesthetized rats. These elevations were partially suppressed by pre-treatment with dexamethasone 12 h prior to sacrifice. We conclude that both tourniquet and leg break stimulate ACTH secretion through pathways in the spinal cord. These pathways are not consistently lateralized between L1 and T10 but are contralateral to the stimulated extremity above T10.

Pre-ovulatory progesterone, the adrenal cortex and the 'critical period' for luteinizing hormone release in rats.

SUMMARY During the day of pro-oestrus in rats showing regular 4-day oestrous cycles, the concentration of progesterone in peripheral plasma increased slowly from 09.30 to 13.30 h and more rapidly during and after the 'critical period' for luteinizing hormone (LH) release to reach a level of 24·4 ng/ml at 21.00 h. Administration of sodium pentobarbitone at 07.00 or 13.30 h (but not at 16.30) on the day of pro-oestrus delayed ovulation and also prevented the rise in progesterone concentration at 21.00 h on that day. Levels were found to be high 24 h later on the evening of the day preceding the delayed ovulation. It is concluded that the major rise during and after the 'critical period' is the result of LH stimulation of ovarian progesterone secretion. The possibility that the gradual increase in peripheral plasma progesterone concentration that occurred before the 'critical period' was due to adrenal secretion and played some role in facilitating the onset of the ovulatory surge of LH was examined. The rise in plasma corticosterone concentration roughly paralleled that of progesterone up to the 'critical period' but the curves for the two steroids later became divergent. Suppression of adrenal activity during pro-oestrus by the administration of dexamethasone phosphate resulted in a blockade of ovulation which could be reversed by the administration of either progesterone or corticotrophin (ACTH). Conversely, blockade of ovulation followed ACTH administration at metoestrus and approximately 50% of animals adrenalectomized or sham-adrenalectomized at metoestrus or dioestrus failed to ovulate at the expected time. In adrenalectomized rats tested 12–15 days after operation, the period of pro-oestrus during which sodium pentobarbitone administration could block ovulation was more prolonged than in intact rats. The possible roles of progesterone of adrenal origin in facilitating LH release and entraining the LH release mechanism to the light—dark rhythm and of progesterone of ovarian origin in ensuring full sexual receptivity are discussed.

THE SELECTIVE TESTICULAR EFFECTS OF CERTAIN BIS-(DICHLOROACETYL) DIAMINES

N,N′-4-Xylylene-bis(N-ethyldichloroacetamide), Compound I,and N,N′-bis (dichloroacetyl)-l,8-octamethylenediamine, Compound II, produced in rats marked testicular weight regression associated with complete arrest of spermatogenesis. Compound II was approximately eight times more active, per mg., than Compound I. At maximal effects the seminiferous tubules consisted merely of a ring of Sertoli cells with spermatogonia interspersed. Leydig cell morphology and androgen production were not altered by antispermatogenic doses of either agent. The weight of the adrenal glands was lowered by high doses of both compounds although the adrenals appeared normal histologically. The plasma corticosterone level of chronically medicated rats was not different from that of control animals. Also, the rise in plasma corticosterone concentration observed two hours after ACTH administration was not altered by prior medication with Compound II. Concurrent injections of 10 r.u. per rat per day of commercial pituitary gonadotroph...