Postnatal maturation patterns of serum corticosterone and growth hormone in rats: effect of chronic thyroxine administration.

The effects of chronic neonatal hyperthyroidism in rats on the ontogenic pattern of serum corticosterone and growth hormone (GH) were studied. Thyroxine (T4) treated and saline injected rat pups were sacrificed under basal and stress conditions. In comparison to saline control animals, daily T4 administration (0.4 micrograms/gram body weight) produced a sustained elevation in basal corticosterone levels by day 12 and a significant elevation of serum corticosterone in response to stress by day 4. The serum GH levels in non-stressed animals were moderately decreased in response to T4 administration as compared to saline injected animals with a greater reduction in GH measured in samples obtained from stressed animals. The results indicate that chronic T4 administration influences the developmental pattern of serum corticosterone and GH under both non-stress and stress conditions.     

Effects of lithium on inducible enzymes of rat liver.

Chronic lithium administration to female rats results in elevation of serum corticoids, lowering of serum glucose and altered induction of liver enzymes. The cortisol induction of tyrosine transaminase is increased selectively over that of tryptophan oxygenase. The glucose induction of glucokinase following a fast is increased by chronic lithium treatment but diminished by acute treatment. These results indicate that lithium may alter the glucose metabolic set-point in rats.     

Effect of testosterone on adrenal corticosteroidogenesis in lithium treated male rats

Lithium chloride at a dose of 200 micrograms/100 g body weight/day given for 21 days caused a significant increase in adrenal weight, adrenal 5-ene-3 beta-hydroxysteroid dehydrogenase (5-ene-3 beta-HSD) activity along with elevation in serum level of corticosterone on the 22nd day in the rat. Administration of testosterone for the last 14 days to lithium treated rats caused a significant decrease in adrenal weight, adrenal 5-ene-3 beta-HSD activity and serum level of corticosterone in comparison to lithium treated animals.     

Neonatal handling enhances contextual fear conditioning and alters corticosterone stress responses in young rats

Previous studies have indicated that neonatal handling influences development of hypothalamic-pituitary-adrenal (HPA) control of corticosterone. In addition, corticosterone influences memory consolidation processes in contextual fear conditioning. Therefore, neonatal handling may affect hippocampal-dependent memory processes present in contextual fear conditioning by influencing the development of HPA control of corticosterone. To investigate the effects of neonatal handling on early learning, rat pups were either handled (15-min removal from home cage) on the first 15 days after birth or left undisturbed in their home cage. Handled rats and nonhandled rats were fear conditioned at 18, 21, or 30 days of age and then tested at two time points--24 h following conditioning and at postnatal day 45. Subsequently, at approximately postnatal day 60, rats were exposed to restraint stress and corticosterone levels were assessed during restraint and recovery. Handled and nonhandled rats did not differ significantly in their freezing response immediately following footshock on the conditioning day. However, when tested for contextual fear conditioning at 24 h following conditioning and at postnatal day 45, handled rats showed more freezing behavior than nonhandled rats. When exposed to restraint stress, handled rats had a more rapid return of corticosterone to basal levels than nonhandled rats. These results indicate that neonatal handling enhances developmentally early memory processes involved in contextual fear conditioning and confirms previously reported effects of neonatal handling on HPA control of corticosterone.     

Lithium action on adrenomedullary and adrenocortical functions and serum ionic balance in different age-groups of albino rats

The aim of the current study was to investigate lithium action on adrenomedullary and adrenocortical functions and on serum ionic balance in rats. Three age-groups of male rats (juvenile: 30 days, adult: 100 days and aged: 3 years) were used. Each age-group of animal was exposed to short- (10 days) and long-term (25 days) treatments with lithium. Each age-group of rat received lithium at a dose 2mEq/kg body weight daily for 10 and 25 days. Each daily dose (2mEq) was divided equally into half (1 mEq) and each half was injected intraperitoneally twice (at 9 am and 9 pm) for both the durations of experiments. Control animals received physiological saline for similar duration of experiments. Thirty animals were used for each age-group and they were divided equally into 6 groups with 5 each. After termination of all the experiments rats were sacrificed and, adrenal glands were quickly dissected out and processed for epinephrine, norepinephrine and corticosterone estimations and, 3 beta-hydroxysteroid dehydrogenase (3 beta-HSDH) activity of the adrenal gland. Blood was drawn from the heart of each rat and, serum was collected and stored at -20 degrees C until assayed for lithium, calcium, sodium, potassium and corticosterone concentrations. The findings revealed that lithium in both short- and long-term treatments was maintained well within the therapeutic range (0.3-0.8 mEq/l) in all the age-groups of rats. This alkali metal caused depletions of both epinephrine and norepinephrine concentrations from adrenal glands, and elevations of corticosterone in both adrenal and blood serum of each age-group of rat (juvenile, adult and aged). Additionally adrenal 3beta-HSDH activity was also increased in all the age-groups of rats irrespective of duration of the treatments. Short-term treatment of lithium elevated only serum K+ level in juvenile and adult rats and, Ca+ level only in adult animals. Significant elevations of serum K+ and Ca+ levels were observed following long-term treatments of lithium in all the age group of rats. No significant change in serum Na+ level was recorded after lithium treatment, irrespective of duration of treatments, in any age-group of rats. The findings suggest that lithium action, in respect of adrenomedullary and adrenocortical functions and, serum ionic balance, may not be largely related to the age-group of rats and that, lithium acts on adrenomedullary activity probably by stimulating the release mechanism of epinephrine and norepinephrine from the adrenal gland of rats, but stimulates adrenocortical activity by stimulating both synthesis (including 3 beta-HSDH activity) and release of corticorterone. Simultaneously, lithium disturbs normal ionic balance by elevating K+ and Ca+ levels in all the age-group of rats. Thus, the antimanic drug certainly disturbs both adrenomedullary and adrenocortical functions and, serum ionic balance in all the age-group of rats.     

Plasma Insulin in Response to Enterostatin and Effect of Adrenalectomy in Rats

Enterostatin has previously been reported to alter serum insulin and corticosterone levels after central administration of the peptide. The purpose of the present study was to investigate the effect of peripheral administration of enterostatin on insulin and corticosterone levels as well as the response of plasma insulin to enterostatin administration in adrena-lectomized rats. Female Sprague-Dawley rats were given a bolus injection intravenously with enterostatin alone or together with glucose. Enterostatin increased basal plasma levels of insulin, but significantly inhibited the increase in plasma insulin stimulated by glucose. Plasma corticosterone levels were not altered after a single intravenous injection of enterostatin. In rats infused chronically with enterostatin, plasma insulin levels were significantly reduced and plasma corticosterone levels were increased. The daily food intake was lower in these rats, but there was no effect on body weight. After adrenalectomy, the responsiveness of plasma insulin to enterostatin infusion was completely abolished. Furthermore, adrenalectomy itself reduced basal plasma levels of insulin and increased plasma levels of endogenous enterostatin. These results suggest that peripheral enterostatin administration produces a similar effect as central infusion of the peptide, and that the glucocorticoid hormones are involved in the regulation of plasma insulin by enterostatin.     

Time-dependent effects of starvation on serum, pituitary and hypothalamic leptin levels in rats

Leptin is produced by white adipose tissue and other cell types and is involved in both short- and long-term appetite control. Here we studied effects of starvation on serum, pituitary and hypothalamic levels of leptin during 72 h period. Each of the starved groups was sacrificed simultaneously with the group of ad libitum fed animals. The progression of the discrete starvation response phases was monitored by testing the blood glucose, free fatty acid, urea and corticosterone levels. Starvation caused biphasic increase in corticosterone and free fatty acid levels, and significant but transient decrease in urea and glucose levels. Starvation also abolished diurnal rhythm of changes in leptin concentrations in serum and hypothalamic and pituitary tissues. Only 6 h starving period was sufficient to lock serum leptin at low levels, whereas 12 h were needed to silence leptin production/secretion in hypothalamus for the whole examined period. In contrast, leptin production by pituitary tissues of starved animals required 24 h to reach minimum, followed by full recovery by the end of starvation period. These results indicate the tissue specific pattern of leptin release and suggest that the locally produced leptin could activate its receptor in pituitary cells independently of serum levels of this hormone.     

Pituitary-adrenocortical axis, serum serotonin and biochemical response after halothane or isoflurane anaesthesia in rabbits

To document the changes in serum serotonin, adrenocorticotrophic hormone (ACTH), corticosterone levels and select biochemical parameters in response to inhalant anaesthesia, 20 New Zealand White (NZW) rabbits were assigned to two treatment groups: halothane and isoflurane. Induction of anaesthesia was achieved using a face mask (3.5% halothane and 4.5% isoflurane in oxygen) followed by endotracheal intubation and maintenance of anaesthesia for 30 min (1.5% halothane and 2.5% isoflurane in oxygen). Blood samples were obtained before anaesthetic induction, and at 1, 10, 30, 60, 120 min and 24, 48 and 72 h after endotracheal intubation. Serum serotonin and corticosterone levels were measured by competitive enzyme immunoassay, ACTH by radioimmunoassay. Serum glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN) and creatinine levels were measured using an automated analyser. Significant increases in serum ACTH and corticosterone levels occurred after halothane administration while serum serotonin levels did not change. An increase in serum corticosterone and serotonin levels occurred in the isoflurane group but no changes in ACTH concentrations were detected. Administration of halothane significantly increased serum glucose, ALT, AST, BUN and creatinine levels. After isoflurane administration, there was a significant increase in serum glucose, AST, BUN and creatinine levels. Based on these results, halothane stimulates the hypothalamic-pituitary-adrenal axis to a greater extent than isoflurane, but isoflurane increases serum serotonin levels. Both anaesthetic agents alter select biochemical parameters. These results should be taken into account when blood samples are evaluated in treated isoflurane or halothane anaesthetized rabbits.     

Lithium accumulation in some endocrine tissues.

Lithium levels were measured in several tissues of rats after oral lithium administration for various periods of time. The lithium levels in the brain approached those of the serum while there was a marked accumulation of lithium in the pituitary and thyroid glands. When lithium was stopped there was no noticeable lag in clearance for any of the tissues examined, with the pituitary maintaining a significant elevation of lithium over the serum levels. Animals receiving lithium had higher levels of adrenal corticosterone under quiescent conditions and higher levels of plasma corticosterone thirty minutes after a brief electric footshock.     

Differential outcomes of unilateral interferences at birth

Behavioural modifications, including modifications of emotional reactivity, can occur following early experience such as handling (manual rubbing). Here, we investigated the effects of unilateral tactile stimulation at an early stage on emotional reactions later on. We handled newborn foals intensively on one side of their body. This early unilateral tactile experience had medium-term effects: the reactions of foals to a human approach, when they were 10 days old, differed according to the side stimulated at birth. Fewer right-handled foals accepted contact with humans, they delayed first contact longer and they evaded approaching humans sooner than did non-handled and left-handled foals. These results raise questions concerning the organization of neonatal care in animals and humans.     

Association Between Na<Superscript>+</Superscript>,K<Superscript>+</Superscript>-ATPase Activity and the Vulnerability/Resilience to Mood Disorders induced by Early Life Experience

There is increasing evidence that early life events can influence neurodevelopment and later susceptibility to disease. Chronic variable stress (CVS) has been used as a model of depression. The objective of this study was to evaluate the interaction between early experience and vulnerability to chronic variable stress in adulthood, analyzing emotional, metabolic and neurochemical aspects related to depression. Pups were (1) handled (10 min/day) or (2) left undisturbed from day 1 to 10 after birth. When the animals reached adulthood, the groups were subdivided and the rats were submitted or not to CVS, which consisted of daily exposure to different stressors for 40 days, followed by a period of behavioral tasks, biochemical (plasma corticosterone and insulin sensitivity) and neurochemical (Na⁺,K⁺-ATPase activity in hippocampus, amygdala and parietal cortex) measurements. Neonatally-handled rats demonstrated shorter immobility times in the forced swimming test, independently of the stress condition. There was no difference concerning basal corticosterone or insulin sensitivity between the groups. Na⁺,K⁺-ATPase activity was decreased in hippocampus and increased in the amygdala of neonatally-handled rats. CVS decreased the enzyme activity in the three structures, mainly in the non-handled group. These findings suggest that early handling increases the ability to cope with chronic variable stress in adulthood, with animals showing less susceptibility to neurochemical features associated with depression, confirming the relevance of the precocious environment to vulnerability to psychiatric conditions in adulthood.     

Escape versus exploratory activity: An interpretation of rats' behaviour in the open field and a light-dark preference test

To test the assumption that dark preference in rats can serve as a measure of emotionality, dark preference was compared with ambulation and defacation in the open field. One group of 80-days-old male rats was handled for seven days; another group remained undisturbed. All animals were tested on each of five successive days in both a light-dark preference situation and an open field. Handled rats ambulated more in the field and stayed less time in the dark than non-handled ones. Significant negative correlations were found for the different days between open field ambulation and dark preference. Correlations between dark preference and open field defacation were positive except on day one. From the first to the second trial dark preference increased in both groups while open field ambulation decreased. The results were considered to support the hypothesis of dark preference as a measure of emotionality.In a second study an investigation was made as to whether high initial activity in a new situation is brought about by exploration or by an escape tendency. Again one group of male albino rats was handled. During testing, half of the handled and half of the non-handled rats had the chance of escaping from the open field into the adjacent home cage. From there the animals had the possibility of re-entering the field. The second half of each group had to stay in the field. These latter animals showed a remarkable decrease in ambulation from the first to the second trial. Rats which had access to their home cages seldom re-entered the field in the first trial. In later trials, however, ambulation in the field increased. Non-handled rats needed more trials before they started investigating the field. It was concluded that this result gives more support to an explanation of initial activity in terms of escape behaviour.     

Neonatal Handling, Sweet Food Ingestion and Ectonucleotidase Activities in Nucleus Accumbens at Different Ages

Neonatal handled rats ingest more sweet food than non-handled ones, but it was documented only after puberty. Here, we studied the purinergic system in the nucleus accumbens, a possible target for the alteration in the preference for palatable food. We measured the ATP, ADP and AMP hydrolysis mediated by ectonucleotidases in synaptosomes of the nucleus accumbens in periadolescent and adult rats from different neonatal environments: non-handled and handled (10 min/day, first 10 days of life). Before adolescence, we found a decreased ingestion of sweet food in the neonatally handled group, with no effect on ATP, ADP or AMP hydrolysis. In adults, we found a greater ingestion of sweet food in the neonatally handled group, with no effect on ATPase or ADPase activities, but a decreased AMP hydrolysis. The nucleus accumbens is a site of intensive interaction between the adenosinergic and dopaminergic systems. Therefore, adenosine may modulate accumbens’ dopamine neurotransmission differently in neonatally handled rats.     

The effect of dexamethasone on plasma glucose and liver glycogen levels in premetamorphic Rana catesbeiana tadpoles and frogs

Premetamorphic Rana catesbeiana tadpoles and adult frogs demonstrate significant elevations in plasma glucose levels following dexamethasone (dex) injections. This response is greatest in the tadpole 24 hr after dex administration and is still detectable at 48 hr. Liver glycogen levels increase in the frog, but not in the tadpole, following daily injections of dex for five consecutive days. The response of the tadpole to dex occurs at a time when hepatic cytosolic glucocorticoid receptors have been observed, but when endogenous corticosterone is absent.     

The influence of long-term melatonin administration on basic physiological and metabolic variables of young Wistar:Han rats

The question of effects of long-term melatonin (MEL) administration have not yet been explained sufficiently, especially its metabolic consequences in young persons and animals. The aim of the present study was to analyze the effects of MEL given during prolonged time (for 3 months) and chronically (for 6 months) at the dose of 4 μg/mL of tap water, on the selected metabolic and hormonal parameters in young female and male Wistar:Han (WH) rats. The weights of selected organs, tissues, body weight gains and food and water intake were registered. Six weeks aged rats were adapted to standard housing conditions and light regimen L:D=12:12 h, fed standard laboratory diet and drank tap water (controls) or MEL solution ad libitum; finally they were sacrificed after overnight fasting. Prolonged MEL administration decreased serum glucose concentration and increased triacylglycerol and malondialdehyde concentration/content in the liver in females. In males MEL increased concentrations of serum phospholipids, corticosterone and liver malondialdehyde. MEL treatment reduced the body weight in both sexes and weight of epididymal fat in males, without any alterations of food and water intake. Chronic MEL administration reduced serum glucose concentration and increased concentration/content of glycogen, triacylglycerol and cholesterol in the liver and glycogen concentration/content in heart muscle in males. In females, the significant rise of serum corticosterone concentration and liver malondialdehyde content was recorded. MEL significantly increased liver weight and decreased thymus weight in males. MEL administration increased temporarily water intake in males, body and epididymal fat weights were similar to that in controls. Body weight of MEL drinking females was reduced in the 1^st half of experiment only; the food and water intake did not differ from control group. The response in WH rats on MEL was more prominent as in the Sprague-Dawley strain (our previous studies). Male rats were generally more affected, probably due to higher daily and total consumption of melatonin.     

Lithium's effects on rat liver glucose metabolism in vivo

Oral administration of lithium carbonate to fed-healthy rats strongly decreased liver glycogen content, despite the simultaneous activation of glycogen synthase and the inactivation of glycogen phosphorylase. The effect seemed to be related to a decrease in glucose 6-phosphate concentration and to a decrease in glucokinase activity. Moreover, in these animals lithium markedly decreased liver fructose 2,6-bisphosphate, which could be a consequence of the fall in glucose 6-phosphate and of the inactivation of 6-phosphofructo-2-kinase. Liver pyruvate kinase activity and blood insulin also decreased after lithium administration. Lower doses of lithium carbonate had less intense effects. Lithium administration to starved-healthy and fed-streptozotocin-diabetic rats caused a slight increase in blood insulin, which was simultaneous with increases in liver glycogen, glucose 6-phosphate, and fructose 2, 6-phosphate. Glucokinase, 6-phosphofructo-2-kinase, and pyruvate kinase activities also increased after lithium administration in starved-healthy and fed-diabetic rats. Lithium treatment activated glycogen synthase and inactivated glycogen phosphorylase in a manner similar to that observed in fed-healthy rats. Glycemia was not modified in any group of animals. These results indicate that lithium acts on liver glycogen metabolism in vivo in at least two different ways: one related to changes in insulinemia, and the other related to the direct action of lithium on the activity of some key enzymes of liver glucose metabolism.     

Effect of Ghrelin Administration on Serum Corticostrone,T<Subscript>3</Subscript>, T<Subscript>4</Subscript> and Some Biochemical Indices in the Turkey (<Emphasis Type="Italic">Meleagridis gallopova</Emphasis>)

Ghrelin is a multifunctional regulatory peptide that has widespread endocrine and metabolic effects in mammals and birds. The present study aimed to investigate the possible effect of ghrelin on blood hormone and biochemical indices in turkey. A total of forty-eight 28 day-old turkeys were divided into three groups for tests. Ghrelin was injected at the onset of the experiment (28-day old birds). Treatment doses were as follows: treatment 1 (control) without injection; treatment 2—50 ng ghrelin/kg body weight (BW); and treatment 3—100 ng ghrelin/kg BW. Two blood samples were taken from the birds, one at 12 h (short-term effect) and the other at 40 days (long-term effect). Blood analyses showed that level of corticosterone increased in response to ghrelin treatments G50 and G100 in samples taken on days 28 and 68 (p?<?0.01). There was an increase in T₄ concentration in the G50 and G100 groups in comparison with the control. Blood glucose increased in response to ghrelin administration, and total cholesterol and triglyceride concentrations decreased in the two samples in response to higher ghrelin dosage (p?<?0.01). In conclusion, the peripheral administration of ghrelin in turkeys may increase levels of serum corticosterone, glucose and T₄. Therefore, total cholesterol and triglyceride may decrease in birds following ghrelin administration. Ghrelin may increase metabolic rate (due to increases in T4) and regulate lipogenesis in poultry species such as turkey.     

Effects of corticosterone deficiency and its replacement on Leydig cell steroidogenesis

Clinical and experimental studies have shown the adverse effects of glucocorticoid deficiency/metyrapone treatment on testicular Leydig cell testosterone production. However, molecular mechanisms that underlie the effects of glucocorticoid deficiency on Leydig cell steroidogenesis are not yet determined. Therefore, the present study was designed to assess the mechanism of this phenomenon. Following metyrapone-induced corticosterone deficiency, serum testosterone, and Leydig cell 14C-glucose oxidation were decreased. StAR mRNA and protein levels were significantly increased in Leydig cells of corticosterone-deficient animals. mRNA levels and the specific activities of P(450)scc and 17beta-HSD were decreased by corticosterone deficiency, whereas the activity and mRNA of 3beta-HSD were increased. Simultaneous administration of corticosterone prevented its deficiency-induced changes in Leydig cells. Our results show that metyrapone-induced corticosterone deficiency impairs Leydig cell testosterone production by decreasing the activities of steroidogenic enzymes and their mRNA expression and glucose oxidation.     

Response of rats to the presence of stressed conspecifics as a function of time of day

The physiological response of nonrestrained rats to the presence of immobilized conspecifics during the beginning of the active period and the inactive period was studied. In immobilized animals concentrations of serum corticosterone (SCS), serum glucose, and liver glycogen, and the activity of liver tyrosine aminotransferase (TAT) during both the active and the inactive periods, were consistent with earlier studies. In nonrestrained rats the presence of immobilized conspecifics induced a significant increase in SCS during the active period, whereas it had no effect during the inactive period. The level of TAT was significantly elevated in the nonrestrained rats only during the inactive period and remained unchanged during the active period. The results demonstrate a physiological influence of stressed rats on unstressed conspecifics and provide evidence for regulation of TAT activity that is dependent on the situation and the time of day.     

The influence of oral corticosterone replacement on plasma prolactin levels of adrenalectomized female rats

The administration of 80 μg of corticosterone/ml of drinking solution to adrenalectomized (ADX) rats resulted in a 24 hour serum corticosterone pattern similar to that of intact animals except that the magnitude of the afternoon-nocturnal surge was one third. Basal plasma prolactin levels and the estrogen-induced afternoon prolactin surge were similar for intact and for ADX animals receiving corticosterone in the drinking solution. Adrenalectomized animals receiving 0.9% NaCl to drink, however, had an afternoon prolactin surge that was significantly lower than that of intact animals while basal levels were similar.