Genetics and phenogenetics of the hormonal characteristics of animals. VII. Correlation between brain serotonin and the hypothalamo-pituitary-adrenal system in domesticated and undomesticated silver foxes during emotional stress

Two groups of silver foxes, selected according their behaviour with respect to man and non-selected ones, were exposed to restriction-induced stress. It was found that changes in the level of brain serotonin and its main metabolite, 5-hydroxyindolacetic acid, and elevation of plasma corticosteroids concentration in domesticated (tame) silver foxes were much less pronounced than in non-domesticated (non-tame) animals. Positive relationship between type of behaviour, brain serotonin metabolism and pituitary-adrenal axis response to stress was observed. It is suggested that such correlative pattern as changed pituitary-adrenal axis responses in domesticated animals may be due to changes in metabolism of controlling this axis brain transmitter serotonin.     

Role of brain noradrenergic mechanisms in disturbing the circadian rhythm of the functioning hypothalamo-hypophyseo-adrenal cortex system in white rats in early ontogeny

The effects of hormone action and disturbance in catecholamine synthesis in the early postnatal ontogenesis on the circadian rhythm in the hypothalamic-hypophysial-adrenocortical system function were compared in the adult albino rat males. Injection of prednisolone on the 17-19th days of life blocked completely the diurnal rhythm of the corticosterone basal level in blood, the rhythm of adrenocortical response to an emotional stressor and to injection of noradrenaline into the brain lateral ventricle in 3-4 month old animals. Injection of an inhibitor of tyrosine hydroxylase, alpha-methyl-p-tyrosine, at the same period resulted in disappearance of the diurnal rhythm of the corticosterone basal level in adult animals, although the rhythm of response to an emotional stressor or injection of noradrenaline into the brain remained unchanged. A conclusion has been reached that disturbances in catecholamine synthesis in the early postnatal period induces long-term changes of predominantly tonic corticosterone secretion, while the hormone action on the circadian rhythm of the corticosterone basal level and stress response is only partly due to changes in noradrenergic regulation of the hypothalamic-hypophysial-adrenocortical system.     

Reactivity of the hypothalamo-hypophyseal-adrenal complex of adult rats after the administration of hydrocortisone to their mothers during pregnancy

The effect of single and repeated injection of hydrocortisone to rats during the last week of pregnancy on the reactivity of the hypothalamic-hypophysial-suprarenal complex of their adult descendants was studied. The reaction of hypophysial-suprarenal system of the adult rats to an amotional stressor and injection of norepinephrine in the brain lateral vesicle was shown to decrease. Under similar experimental conditions the reaction to ether and combined stressors, as well as to intraventricular injection of 5-HT or carbocholine resembled that in the control animals. It is suggested that hydrocortisone injected during the prenatal period exerts, to a certain extent, the selective influence on the central adrenergic mechanisms the changes in which may serve as one of the causes of decrease in emotional reactivity of adult animals.     

Brain monoamines and the hypophyseo-gonadal system of adult rats after the androgenization of their mothers during pregnancy

The brain noradrenaline system and its involvement in the control of the hypothalamic-hypophysial-gonadal complex were studied on 3 month old Wistar rats, which descended from the mothers treated with testosterone propionate on the 16th and 18th day of pregnancy. A season-independent weakening of the activating effect of noradrenaline, introduced into the brain lateral ventricle on the estradiol and testosterone content of the peripheral blood has been shown, compared with the descendants of the mothers treated with oil at the same times of pregnancy. Unlike noradrenaline, the intraventricular introduction of serotonin or dopamine was accompanied by a similar activation of the hypophysial-gonadal system in the descendants from both the androgenized and control mothers. In the descendants from the former, the thermal reaction to the intraventricular introduction of noradrenaline underwent changes as well. A conclusion is reached that testosterone propionate, introduced during the prenatal period, exerts a long-term and to a certain extent, selective and generalized effect on the developing brain noradrenaline system. In the rats, the critical period for the disturbance in androgen balance influence on the noradrenaline mechanisms of brain is timed to no later than the 18th day of prenatal development.     

The effect of serotonin given into the lateral ventricle of the brain on serum TSH level in normal and thyroxine-blocked rats

The effect of serotonin given into the lateral ventricle of the brain in rats was investigated. Serotonin was solved in artificial cerebrospinal fluid and administered in three doses: 250 microgram, 50 microgram, 10 microgram. Only the highest dose of serotonin caused a statistically significant increase in serum TSH level 0.5 h after the injection. The possible role of serotonin in the blocking mechanism of thyroid hormones on TSH secretion was also taken into consideration. 50 microgram of serotonin significantly strengthened the lowering effect of 1-thyroxine given 0.5 h before on serum TSH level.     

Cardiovascular effects of intraventricular injection of FMRFamide, Met-enkephalin and their common analogues in the rat

The molluscan neuropeptide, Phe-Met-Arg-Phe-NH2 (FMRFamide), the mammalian opioid peptide met-enkephalin, and their common analogues, met-enkephalin-Arg6-Phe7 (YGGFMRF) and Tyr-Gly-Gly-Phe-Met-Arg-Phe-amide (YGGFMRFamide), were injected into the lateral ventricle of the rat; the cardiovascular effects were studied. FMRFamide caused a rapid, transient elevation in blood pressure accompanied by a great increase in pulse pressure. These effects were followed by secondary increases in blood and pulse pressures. Met-enkephalin produced an initial reduction in blood pressure which was followed by a gradual increase at the higher of two test doses (300 nmole). Injection of YGGFMRF resulted in a gradual increase in blood pressure. This response resembled that to met-enkephalin. The initial response to YGGFMRFamide was similar to that to FMRFamide: increases in both blood and pulse pressures after injection. However, the secondary effect of YGGFMRFamide, a prolonged reduction in blood pressure, was not produced by FMRFamide. These results suggest that the initial excitatory cardiovascular responses may be due to the presence of the C-terminal amide. All of the cardiovascular effects of injecting these peptides into the lateral ventricle were abolished by pre-treatment with naloxone in a dose that, itself, produced no cardiovascular changes. In conclusion, these peptides seem to act via the naloxone sensitive opiate receptors in the rat brain.     

The activity of the monoaminergic systems of the rat hypothalamus in acute stress after chronic stressing]

The influence of chronic stress (footshock combined with randomized light flashes) on acute stress-induced (immobilization) release of noradrenaline, dopamine and serotonin in rat lateral hypothalamus was assessed by microdialysis. The chronic stress resulted in an increase and prolongation of the acute stress-induced release of noradrenaline but not of dopamine and serotonin. The increased rate of accumulation of dioxyphenylacetic acid and unchanged accumulation of homovanillic acid (dopamine metabolites) and dopamine during and after the acute stress in chronically stressed animals reflect a rise of synthetic activity of catecholaminergic systems in response to acute stress and reuptake increase. Marked stress-induced increase in hydroxyindoleacetic acid in chronically stressed rats without any changes in the ST dynamics may be regarded in a similar way. A significant increase in potassium-stimulated release of all the studied monoamines was found while their basal level remained unchanged. The conclusions was made that the hyperergic release of neurotransmitters may be the basis of an inadequate response of animals to acute stress, i.e., one of the neurotic symptoms.     

Effects of insulin and streptozotocin-induced diabetes on brain tryptophan and serotonin metabolism in rats

Previous work by other authors has shown hat insulin administration increases brain tryptophan levels and serotonin (5–HT) metabolism. The present study partially replicates these results and tests whether these effects could be due to insulin-induced hypoglycemic stress, since stressers such as immobilization or food deprivation also increase brain tryptophan and 5-HT metabolism. Ingestion of a dextrose solution by rats administered insulin (2 I.U./kg) prevents the extreme fall in blood glucose concentration and rise in plasma corticosterone following insulin injections alone. This treatment, however, produces a larger increase in brain tryptophan (30%) than insulin-injected rats allowed only tap water. The greater accumulation of brain tryptophan may reflect an additive effect of the endogenously released insulin to that exogenously administered, since ingestion of the dextrose solution could trigger insulin secretion. In addition, brain tryptophan and 5-HT metabolism were measured in streptozotocin-diabetic rats maintained on several different feeding schedules to control for the effects of hyperphagia. All groups of diabetics showed significant decreases of approx 30% in brain tryptophan concentrations, while 5-HT metabolism was unchanged. This deficit in brain tryptophan is reversed within 2 h after insulin administration (2 I.U./kg). These results indicate that changes in brain tryptophan and 5-HT metabolism following insulin injections are not due to hypoglycemic stress, and that brain tryptophan is low in diabetics but increases above normal after administration of insulin. The results are discussed with respect to the effects of insulin on plasma levels of the neutral amino acids and a possible direct effect of insulin on the uptake of tryptophan by brain.     

EFFECTS OF IMMOBILIZATION AND FOOD DEPRIVATION ON RAT BRAIN TRYPTOPHAN METABOLISM

Abstract— Withdrawal of food or immobilization both led to changes in rat brain tryptophan metabolism. Brain tryptophan and 5-hydroxyindolylacetic acid concentrations both increased while changes in 5-hydroxytryptamine were much smaller. Changes were greater upon withdrawal of food. The brain tryptophan change did not appear merely to reflect an overall increase of brain amino acid concentrations, brain tyrosine concentration being only slightly increased by food withdrawal and significantly decreased upon immobilization. Plasma tryptophan did not increase. The changes in brain indole metabolism were not abolished by adrenalectomy. Results are discussed in relation to the regulation of brain serotonin metabolism.     

Reactivity of the hypothalamo-pituitary-adrenocortical system in rats with hereditary arterial hypertension

The function of hypothalamo-hypophyseal-adrenocortical system was studied in rats with inherited stress-sensitive arterial hypertension (ISSAH). The rats have been bred from the outbred Wistar strain. It was found that plasma corticosteroid level in ISSAH rats was lower after immobilization stress and higher after stress induced by a combination of stress-factors (ether, 0.7 ml blood loss, novel situation), as compared to Wistar rats. ISSAH rats also showed a reduced reaction to intracerebroventricular noradrenaline (10 micrograms) injection. It was concluded that the changes of noradrenergig brain mechanisms can be responsible for the alterations in the central regulation of blood pressure and adrenocortical function in ISSAH rats.     

Adaptogenic role of serotonin in dogs coming out of an experimental neurosis

In a study carried out on dogs by means of alimentary salivary conditioned reflexes, it was found out that serotonin injection into the anterior limbic cortex and the action of neurogenous stimuli lead neither to the development of experimental neurosis nor to the usual for the neurosis increase of blood serotonin level. At the treatment of experimental neurosis by small doses of 5-oxytryptophan, the therapeutic effect of this serotonin predecessor appeared only in the days of its injection. In the subsequent period, the neurotic changes in the higher nervous activity continued, and the blood serotonin level remained increased. These data as well as materials earlier obtained on the increase of the blood serotonin level at neurosis in dogs, give reason to consider the increase of activity of the serotoninergic system at neurosis as one of adaptogenous factors contributing to the coming out of neurosis.     

Effect of restraint stress on rat brain serotonin

Restraint-induced stress in rats was found to enhance steady state concentrations of whole brain and hypothalamic serotonin, at 1,2 and 4 h after immobilization. The increase was maximal at 1 h and tended to decline thereafter. The rate of accumulation of rat brain serotonin, in pargyline pretreated animals, was significantly enhanced after restraint stress. Bilateral adrenalectomy and metyrapone, an endogenous corticoid synthesis inhibitor, failed to affect restraint stress (1h)-induced increase in rat brain serotonin levels. Thus restraint stress-induced autoanalgesia and potentiation of the pharmacological actions of several centrally acting drugs, in rats, are serotonin-mediated responses. The results also indicate that restraint stress-induced effects on rat brain serotonin are not dependent on endogenous corticoid activity.     

Development of the hormonal reaction to stress in the ontogenesis of the baboon Papio hamadryas

The hormonal reaction of adrenal and gonadal glands of baboons at various ages was studied under 2 hr immobilization stress condition. Concentrations of cortisol, 11-deoxycortisol, 17-hydroxypregnenolone, dehydroepiandrosterone and testosterone were determined by radioimmunoassay in the monkey blood plasma at different times during the stress reaction. A more pronounced reaction of adrenal cortex was shown in 1 year old baboons. The peak of cortisol level in immature monkeys under stress conditions was registered much earlier than in adult monkeys.     

Collagen metabolism during immobilization and electropuncture

The indices of collagen metabolism (free, peptide- and protein bound hydroxyproline) as well as blood plasma proteolytic activity were studied in repeated immobilization (up to 5 days) and skin electropuncture (up to 8 days) in rats. Repeated immobilization (strong stress) steadily increased the contents of free oxyproline and induced undulating changes in the level of other indices under study. Electropuncture (slight stress) produced a short-term increase in free oxyproline blood plasma level. Preliminary and simultaneous electropuncture prevented profound changes in collagen metabolism during immobilization.     

Footshock-induced changes in brain catecholamines and indoleamines are not mediated by CRF or ACTH

Stressful treatments have long been associated with increased activity of brain catecholaminergic and serotonergic neurons. An intracerebroventricular (icv) injection of the corticotropin-releasing factor (CRF) also activates brain catecholaminergic neurons. Because brain CRF-containing neurons appear to be activated during stress, it is possible that CRF mediates the catecholaminergic activation. This hypothesis has been tested by assessing the responses in brain catecholamines and indoleamines to footshock in mice pretreated icv with a CRF receptor antagonist, and in mice lacking the gene for CRF (CRFko mice). Consistent with earlier results, icv administration of CRF increased catabolites of dopamine and norepinephrine, but failed to alter tryptophan concentrations or serotonin catabolism. A brief period of footshock increased plasma corticosterone and the concentrations of tryptophan and the catabolites of dopamine, norepinephrine and serotonin in several brain regions. Mice injected icv with 25 microg alpha-helical CRF(9-41) prior to footshock had neurochemical responses that were indistinguishable from controls injected with vehicle, while the increase in plasma corticosterone was slightly attenuated in some experiments. CRFko mice exhibited neurochemical responses to footshock that were indistinguishable from wild-type mice. However, whereas wild-type mice showed the expected increase in plasma corticosterone, there was no such increase in CRFko mice. Similarly, hypophysectomized mice also showed normal neurochemical responses to footshock, but no increase in plasma corticosterone. Hypophysectomy itself elevated brain tryptophan and catecholamine and serotonin metabolism. Treatment with ACTH icv or peripherally failed to induce any changes in cerebral catecholamines and indoleamines. These results suggest that CRF and its receptors, and ACTH and other pituitary hormones, are not involved in the catecholamine and serotonin responses to a brief period of footshock.     

侧脑室微量注射大麻素受体拮抗剂对orexin-A诱导大鼠能量代谢改变的影响及潜在机制研究

目的:探讨大麻素1型受体(CB1)抑制剂利莫那班对下丘脑外侧区(LHA)微量注射orexin-A诱导的小鼠能量代谢及相关行为变化改变的影响。方法:通过侧脑室微量注射(icv)利莫那班,同时LHA微量注射orexin-A,测量小鼠能量代谢、自主运动的变化,杏仁核(CeA)内多巴胺释放能力以及小鼠摄食量的变化。结果:侧脑室微量注射利莫那班可减弱因LHA微量注射orexin-A引起的小鼠能量代谢变化,降低小鼠自主运动,并且减弱小鼠CeA内多巴胺释放能力。注射(icv)利莫那班未改变LHA微量注射orexin-A所诱导的摄食量增多。此外,LHA双侧注射利莫那班可阻断LHA内注射orexin-A对运动活性的促进作用,但不影响小鼠的摄食量。结论:大麻素受体涉及orexin-A诱导的小鼠中脑边缘系统多巴胺系统活化的调控,对能量代谢及自主运动也有影响,但对食物摄入的调节无明显影响。     

Effects of 5,7-dihroxytryptamine administered supraspinally or spinally on the blood glucose level in D-glucose-fed and immobilization stress models

5,7-Dihydroxytryptamine (5,7-DHT) is a neurotoxin which causes the depletion of serotonin. Moreover, the serotonergic system is the regulator of the blood glucose level. However, the role of centrally located serotonergic system in blood glucose regulation after D-glucose feed and immobilization (IMO) stress was not clearly characterized yet. Thus the present study was designed to examine the effect of 5,7-DHT administered intracerebroventricularly (i.c.v.) or intrathecally (i.t.) on the blood glucose level in D-glucose-fed and immobilization stress models. Mice were pretreated once i.c.v. or i.t. with 5,7-DHT (from 10 to 40?µg) for 3 days and D-glucose (2?g/kg) was fed orally. The blood glucose level was measured at 0, 30, 60 and 120?min after D-glucose feeding and immobilization stress initiation. We found that i.c.v. or i.t. pretreatment with 5,7-DHT attenuated the blood glucose level in both animal models. D-glucose feeding causes an increase in plasma insulin level, whereas the plasma corticosterone level was downregulated in the D-glucose-fed model. The i.c.v. or i.t. pretreatment with 5,7-DHT alone slightly increased the plasma corticosterone level. In addition, the i.c.v. or i.t. pretreatment with 5,7-DHT caused a reversal of the downregulation of plasma corticosterone level induced by D-glucose feeding, whereas immobilization stress causes an increase in plasma corticosterone and insulin levels. The i.c.v or i.t. pretreatment with 5,7-DHT attenuated the immobilization stress-induced plasma corticosterone and plasma insulin levels. Our results suggest that supraspinal and spinal depletion of serotonin appears to be responsible for the downregulation of blood glucose level in both D-glucose-fed and immobilization stress models.     

Role of the brain neurochemical systems in altering the reactivity of the hypophyseal-adrenal system in the gray rat selected for behavior

Studies have been made of the interrelationship between brain monoaminergic system and pituitary-adrenal function in two groups of the grey rat Rattus norvegicus Berk. One group consisted of non-aggressive rats selected for lack of agonism towards experimentator, the other one included aggressive animals. Domesticated animals exhibited the decreased reaction of the pituitary-adrenocortical complex to emotional stress as well as the decreased response of the endocrine system during stimulation of noradrenaline or serotonin mechanisms of the brain. In addition, noradrenaline and serotonin content of the brain decreased in domesticated rats during emotional stress to a lower extent, as compared to that in aggressive ones. Therefore, one of the sources of correlational changes in the activity of the pituitary-adrenocortical complex during selection for domesticated behaviour is the effect of selection on neurochemical, in particular monoaminergic systems of the brain.     

Reorganization of monoaminergic systems in the earthworm,Eisenia fetida,following brain extirpation

The present study describes the major aspects of how monoaminergic (serotonin, dopamine) systems change in the course of regeneration of the brain in the earthworm (Eisenia fetida), investigated by immunocytochemistry, HPLC assay, and ligand binding. Following brain extirpation, the total regeneration time is about 80 days at 10 degrees C. On the 3rd postoperative day serotonin, and on the 11th postoperative day tyrosine hydroxylase-immunoreactive neurons can be observed in the wound tissue. Thereafter the number of the immunoreactive cells increases gradually, and by the 76th-80th postoperative days all serotonin- and tyrosine hydroxylase-immunopositive neurons can be found in their final positions, similarly to those observed in the intact brain. Labeled neurons located in the dorsal part of the regenerated brain appear earlier than the cells in lateral and ventral positions. Both serotonin- and tyrosine hydroxylase-immunoreactive neurons of the newly formed brain seem to originate from undifferentiated neuroblasts situated within and around the ventral ganglia and the pleura. Dopaminergic (tyrosine hydroxylase-immunoreactive) elements may additionally derive from the proliferation of neurons localized in the subesophageal ganglion and the pharyngeal nerve plexus. Following brain extirpation, both serotonin and dopamine levels, assayed by HPLC, first increase in the subesophageal ganglion; by the 25th day of regeneration, the monoamine content decreases in it and increases in the brain. Hence it is suggested that monoamines are at least partly transported from this ganglion to the regenerating brain. At the same time, (3)H-LSD binding can be detected in the regenerating brain from the 3rd postoperative day, showing a continuous increase until the 80th postoperative day, suggesting a guiding role of postsynaptic elements in the monoaminergic reinnervation of the newly formed brain.     

Neuroendocrine reactions to intracerebroventricular injections of arginine-vasopressin in prenatally stressed rats

We studied the effect of central vasopressinergic stimulation on the functions of the hypothalamo-pituitary-adrenal and hypothalamo-pituitary-gonadal axes in mature offsprings of female rats stressed during the last week of pregnancy (daily immobilization for 1 h). Experiments were carried out on unanesthetized rats; the blood samples were taken 20 and 40 min after intracerebroventricular injections of arginine-vasopressin (AVP). Twenty minutes after infusion of 0.5 ng of this neuropeptide dissolved in 2 μl of isotonic NaCl solution into the III cerebral ventricle, the adrenocortical reaction in prenatally stressed males was 50% smaller than that in normal animals; on the 40th min, it continued to develop but remained weaker. In prenatally stressed females, the adrenocortical reaction to central vasopressinergic stimulation was weakened. Arginine-vasopressin-induced increases in the level of corticotropin in the blood were nearly identical in both prenatally stressed and normal rats (males and females). The level of testosterone in the blood of prenatally stressed and normal males dropped sharply 20 min after intracerebroventricular injection of AVP and, on the 40th min, remained significantly lower than the basal level in males of both studied groups; prenatal stress did not influence these alterations. Our data show that vasopressinergic control is weakened in prenatally stressed male rats, and this is a significant probable reason for the decrease in the stress reactivity of the hypothalamo-pituitary-adrenal system in these animals. Neirofiziologiya/Neurophysiology, Vol. 39, No. 6, pp. 453–457, November–December, 2007.