Changes In Plasma Corticosterone Levels Research Articles

Acute cold-induced thermogenesis in neonatal chicks ( Gallus gallus)

Mechanisms of thermogenic responses that play a role to maintain homeothermy during an early stage of neonatal chicks on acute cold exposure are scarcely studied as hatchlings are believed to be poikilothermic. However, chicks can attain the homeothermy during their subsequent growth after hatching. To identify thermogenic responses during neonatal stages of chicks ( Gallus gallus) on acute cold exposure (12 °C, 3 h), changes in plasma corticosterone levels, thermogenesis, gene transcripts (avUCP and avPGC1α) in skeletal muscles ( pectoralis superficialis and gastrocnemius) and mitochondrial substrate oxidation enzyme activities in dissected tissues of 1- and 4-d-old chicks were studied. Results revealed that 1-day-old neonatal chicks were particularly vulnerable to cold exposure and were hypothermic. However, 4-d-old cold-exposed chicks maintained thermostability with significantly higher plasma corticosterone levels, oxygen consumption, heat production, and increased mitochondrial substrate oxidation enzyme activities (CS and 3HADH) in different dissected tissues. Analysis of gene transcripts for avian peroxisome-proliferator-activated receptor-γ co-activator-1α (avPGC1α) and avian uncoupling protein (avUCP) in skeletal muscles revealed no significant change between cold-sensitive (1-d-old) and cold-tolerant (4-d-old) neonatal chicks, and failed to explain the enhanced thermogenesis and tolerance to acute cold. Additionally, avPGC1α gene transcripts were not correlated with the increased enzyme activities of CS or 3HADH in skeletal muscle. In conclusion, these data suggest the possible role of HPA-axis in cold-tolerant neonatal chicks to modulate substrate mobilization and oxidation. The thermogenic mechanisms based in part upon the increased capacity for mitochondrial substrate oxidation in different tissues are associated with enhanced heat production to attain homeothermy and acquire tolerance to acute cold exposure during an early stage of neonatal chicks.

Impairments in water maze learning of aged rats that received dextromethorphan repeatedly during adolescent period

Dextromethorphan (DM), an over-the-counter cough suppressant, has been recently used as a drug of abuse by teenage groups in some countries, such as the United States, Canada, and Korea. We previously showed that repeated administration of DM, a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptors, impairs spatial learning performance in adolescent rats. In the present study, long-term adverse effects of repetitive DM use at adolescence were examined in rats. Male and female Sprague-Dawley rat pups received either intraperitoneal DM (40 mg/kg) or saline daily during postnatal days 28-37, and were then subjected to the Morris water maze task at the age of 18 months. Expression levels of NMDAR1, functional subunit of NMDA receptors, in the prefrontal cortex and the hippocampus were examined by Western blot analysis. Changes in plasma corticosterone levels responding to stress were determined by radioimmunoassay. DM-experienced male rats exhibited deficits in the probe trial, and female rats in the initial learning and the reversal training, in water maze performance. Expression levels of NMDAR1 in the brain regions were significantly increased in DM-experienced rats, compared to control rats. Stress-induced increases in plasma corticosterone levels were blunted both in male and female DM rats. The results suggest that repeated administration of DM at high doses during adolescent period may induce permanent deficits in cognitive function and that increased expression of NMDAR1 in the prefrontal cortex and the hippocampus may take a role in DM-induced memory deficits.

Sex Differences in Steroid Modulation of Ethanol Withdrawal in Male and Female Rats

We investigated the actions of the neuroactive steroid, pregnanolone [corrected] and the ovarian steroid, 17beta-estradiol, on seizure expression during two time points of ethanol withdrawal (EW). Both steroids can exert rapid, nongenomic actions on the brain that include modulation of seizure activity. Because their basal levels differ in adult males and females and a major symptom of EW is increased seizure risk, we wanted to determine whether these steroids were anticonvulsant during EW. Rats were made ethanol-dependent by administration of 6% ethanol in a nutritionally complete liquid diet for 14 days. After removal of the ethanol-containing diet, EW and paired control rats were tested at 1 or 3 days for seizure responses to pentylenetetrazol. Consistent with previous reports, females seemed to have recovered from EW more quickly than males. We observed significant sex differences in responses to the steroids, primarily at 3 days EW. Pregnanolone afforded protection against seizures with larger effects during EW than in control conditions and greater effects in female than male rats. In contrast, effects of estradiol were mixed. Some responses of ovariectomized female rats were similar to intact females, whereas other responses were more similar to males. Our behavioral findings are consistent with observed EW-induced changes in plasma corticosterone levels, showing persistent elevations in male but not female rats. These results support and extend earlier findings suggesting that although the hormonal milieu influences EW, innate differences in brain structure between the sexes also contribute to sex differences in EW.

Alteration of hippocampal cell proliferation in mice lacking the beta 2 subunit of the neuronal nicotinic acetylcholine receptor.

Adult hippocampal neurogenesis declines with age in parallel with decreased performance on a variety of hippocampal-dependent tasks. We measured the rate of cellular proliferation in the hippocampus of mice lacking the beta 2-subunit of the nicotinic acetylcholine receptor (beta 2-/- mice) at three ages: young adult (3 months old), fully adult (7-10 months old), and aged (22-24 months old). Consistent with previous studies, we observed an age-related decline in hippocampal proliferation in both groups. However, in fully adult beta 2-/- mice a 43% reduction of granule cell proliferation was detected compared to age-matched controls. This was accompanied by a significant decrease in dentate gyrus area/section and the length of the granule cell layer in beta 2-/- mice. These alterations were not the result of a change in plasma corticosterone levels or expression of the neurotrophic factor BDNF in the dentate gyrus, two known regulators of hippocampal cell proliferation. Similarly, there was no increase in gliosis, abnormal myelination, or apoptotic cell death in the beta 2-/- animals, although there was a significant shift in the location of apoptotic cells in the dentate gyrus indicative of a change in neuronal survival. These results suggest that the beta 2-subunit containing nicotinic acetylcholine receptors play an important role in regulating cell proliferation in the hippocampus and that endogenous acetylcholine may act to oppose the negative effects of normal aging and stress on cellular proliferation.

THE EFFECTS OF LOSARTAN AND IMMOBILIZATION STRESS ON HEART RATE VARIABILITY AND PLASMA CORTICOSTERONE LEVELS IN RATS

In this study, the effects of losartan, an angiotensin II receptor antagonist, on heart rate variability and the changes of plasma corticosterone levels caused by immobilization stress were investigated. Losartan (3 mg/kg, p.o.) significantly prevented increases in plasma corticosterone levels in both losartan+acute stress and losartan+chronic stress groups. But, losartan did not prevent the diminution of the power of heart rate variability caused by stress. Our results supported the idea that the renin-angiotensin system is also involved in the stress--induced cardiovascular response, besides the autonomic nervous system. But, the effects of losartan on heart rate variability remained controversial

The effect of transdermal corticosterone application on plasma corticosterone levels in pregnant Lacerta vivipara

Relationships between hormones and behaviour can be explored by altering endogenous hormone levels, often through implantation of silastic tubing or osmotic pumps filled with a hormone or its agonists or antagonists. However, organisms in sensitive life-history stages (such as pregnancy) may be adversely affected by the surgical procedures associated with these manipulations, necessitating use of non-invasive techniques. We demonstrate that the application of a sesame oil–corticosterone mixture to the skin of pregnant female common lizards ( Lacerta vivipara) elevates plasma levels of the hormone. Pregnant female L. vivipara were captured and treated daily for 1–20 days with the sesame oil–corticosterone mixture (experimental group) or with vehicle only (control group). Blood samples were collected and analyzed for corticosterone by radioimmunoassay. Baseline plasma corticosterone levels were elevated within 1 h in the experimental group. Similar levels (≈145 ng/ml) were found over the subsequent 2 days, and by day 5 had risen significantly higher (≈281.9 ng/ml), where they remained for the duration of the experiment. These increases are comparable to those found in other species using related techniques. No significant changes in plasma corticosterone levels occurred in the control group. Finally, corticosterone levels also were determined for untreated females that were captured, held overnight, sampled, and released to access to the natural range of basal corticosterone levels. Basal plasma levels of corticosterone in pregnant females varied among individuals independently of female body size or corpulence.

Gyrus cinguli transection abolishes delta-opioid receptor-induced gastroprotection and alters alpha 2 adrenoceptor activity in the lower brainstem in rats

Previously, using the acidified ethanol-induced ulcer model in rats, we demonstrated that the mainly vagus-dependent gastroprotective effect of intracerebroventricularly injected clonidine was mediated by β-endorphin release in the lower brainstem. Presently, retroarcuate transections were used to evaluate the contribution of forebrain β-endorphinergic projection in this mechanism. Since the transection trajectory affected the cingulate cortex and other forebrain structures, matching lesions were also performed. In control and sham-operated rats intracisternal injection of clonidine and the direct opioid receptor (delta type) stimulant peptide ( d-Ala 2, d-Leu 5)-enkephalin caused a potent and fully naloxone-reversible (i.e. opioid receptor-mediated) protection against acidified ethanol-induced mucosal damage. In gyrus cinguli-transected rats (as well as in groups with midline hippocampal, thalamic and hypothalamic lesions) gastric mucosal protection induced centrally by direct delta-opioid receptor stimulation in the lower brainstem was completely abolished. The protective effect of clonidine was significantly reduced but it was still present in these animals. The residual protection by clonidine was naloxone-resistant, i.e. independent of an opioid mediation. Transections of the cingulate gyrus as well as thalamic but not the retroarcuate transections elevated plasma corticosterone levels. The changes seen in the clonidine/opioid-induced gastroprotection did not show any correlation with the changes in plasma corticosterone levels. It was concluded that (i) the transection of the cingulate cortex strongly influences the neural input to the nucleus tractus solitarii–dorsal motor vagal nucleus complex that is required for the activation of gastroprotective vagus outflow by delta-opioid receptor stimulation; (ii) the transection uncovers a direct, clonidine-induced gastroprotective pathway which is probably suppressed in intact animals.

Effect of Serotonin Inhibition on Glucocorticoid and Mineralocorticoid Expression in Various Brain Structures

Many studies have shown the existence of functional interactions between central neurotransmitter systems and the hypothalamo-pituitary adrenal axis. Mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) are regulated by multiple factors including glucocorticoids themselves. Neurotransmitters such as serotonin (5-hydroxytryptamine: 5-HT) can regulate brain corticosteroid receptors in a complex way. The present study examined the short-term (48 h) effects of parachlorophenylalanine (PCPA), a drug which specifically inhibits 5-HT synthesis, on corticosteroid receptor levels and on the expression of their respective messenger ribonucleic acids (mRNA) in the rat hippocampus, hypothalamus and brain stem. The study was performed in bilaterally adrenalectomized animals, in order to avoid potential drug-induced changes in plasma corticosterone levels, which could secondarily regulate MR and GR. Short-term inhibition of 5-HT synthesis by PCPA significantly increased the number of hippocampal MR-binding sites. PCPA treatment did not alter the number of GR-binding sites in the hippocampus, hypothalamus and brain stem. We observed no change in the affinities of GR and MR sites in all the structures studied. In PCPA-treated rats, restoration of control 5-HT levels by injection of its immediate precursor, 5-hydroxytryptophan (5-HTP) brings the number of hippocampal MR-binding sites back to control levels. It can therefore be concluded that the increase in number of MR-binding sites induced by acute PCPA treatment is dependent on the decrease in 5-HT levels. The increase in hippocampal MR binding sites was correlated with an induction of their messengers, suggesting that 5-HT modulates the synthesis of MR protein. Although PCPA did not modify the number of hippocampal GR-binding sites, a decrease in hippocampal GR mRNA expression was observed. This study shows that 5-HT inhibits hippocampal mineralocorticoid receptor synthesis and that this effect is not mediated by changes in corticosterone hormone secretion, and illustrates the existence of complex mechanisms for corticosteroid receptor regulation in the hippocampus.

The Inhibitory Effect in Experimental Autoimmune Encephalomyelitis by the Immunomodulatory Drug Linomide (PNU-212616) is not Mediated via Release of Endogenous Glucocorticoids

The immunomodulatory drug Linomide (PNU-212616) is an efficient inhibitor of experimental autoimmune encephalomyelitis (EAE) and a variety of other models of autoimmunity. The mechanism of action of the drug is, however, incompletely resolved. It was recently suggested that Linomide might exert its immunomodulatory activity by stimulation of the hypothalamic-pituitary-adrenal axis. To investigate the relevance of this mechanism of action, we monitored the plasma levels of endogenous corticosterone after treatment with Linomide, and also directly compared the inhibitory activity of the drug on acute EAE induced in sham or adrenalectomized SJL/N mice. Treatment with Linomide resulted in a dose related inhibition of EAE in line with previously reported results. Upon onset of clinical signs of EAE, there was a 7–10 fold elevation of plasma corticosterone from the normal baseline level. Administration of Linomide did however not by itself result in any change in plasma corticosterone levels, neither at the pre-symptomatic phase of the disease nor during acute short term treatment. In adrenal ectomized animals immunized for EAE, paralytic disease developed rapidly and was of a more severe and fatal nature as compared to sham-operated controls. Treatment with Linomide had a profound inhibitory effect on development of paralytic disease in both the ectomized and sham-operated groups. These results strongly suggest that Linomide does not exert its immunomodulatory activity via the release of endogenous glucocorticoids.

Lack of effect of endogenous corticosteroids on the acute inflammatory reaction (EDEMA) induced by Bothrops jararaca venom (BjV) in rats

Intraplantar injection of 5 or 10 μg of BjV caused local edema in rats that was not affected by ablation of adrenal glands. In addition, no changes in plasma corticosterone levels were observed. Simultaneous injections of the venom into both hindpaws of normal animals, or injections made at varying intervals, resulted in local inflammatory reactions of comparable time-course development and analogous magnitude. These data might be related to an inability of the venom to evoke secretion of corticosteroids.

Acute blockade of corticosterone secretion decreases the psychomotor stimulant effects of cocaine

Previous reports have shown that long-term blockade of corticosterone secretion, by either adrenalectomy or repeated treatment with an inhibitor of corticosterone synthesis, metyrapone, profoundly reduces sensitivity to drugs of abuse. In this report we investigated whether acute blockade of corticosterone secretion has similar effects. Animals received a single injection of metyrapone (50 mg/kg SC) and were tested for their locomotor response to cocaine (15 mg/kg IP) 3 hours later. Acute metyrapone treatment reduced the locomotor response to cocaine by about 50%, and this effect was reversed by corticosterone (20 mg/kg SC). The behavioral effects of these treatments paralleled changes in plasma corticosterone levels 20 minutes after an injection of cocaine. Despite the differences in behavior and corticosterone levels, the brain levels of cocaine in these groups did not differ. These results indicate that the behavioral effects of cocaine can be modified by an acute pharmacological manipulation of corticosterone secretion.

Evidence for a role of neurosteroids in modulation of diurnal changes and acute stress-induced corticosterone secretion in rats.

The neurosteroid allopregnanolone has been shown to be a potent ligand of gamma-aminobutyric acid (GABA)-A receptors and enhances its receptor-mediated inhibitory events. Since central GABA plays a major inhibitory role, via GABA-A receptors, in hypothalamic-pituitary-adrenal (HPA) function in rats, the present study has evaluated the effect of passive immunoneutralization of allopregnanolone on diurnal changes in corticosterone secretion and acute stress-induced corticosterone secretion in rats. In the first protocol, four groups of male rats (prepubertal, fertile, castrated adult and aged) and three groups of female rats (prepubertal, fertile at different phases of the estrous cycle and aged) were studied. Rats were injected intracerebroventricularly (i.c.v.) with 10 microliters anti-allopregnanolone serum or 10 microliters normal rabbit serum (control) 24 h before exposure to an acute cold swimming stress, and sacrificed either before stress or after 5 min stress. In the second protocol, fertile male or female rats at diestrus II were injected i.c.v. with anti-allopregnanolone serum or normal rabbit serum and sacrificed on the following day at 10.00 or 18.00. Truncal blood samples were collected for measuring plasma corticosterone. Our results showed that there was no significant difference in basal plasma corticosterone levels between antiserum-treated and control rats of both sexes. However, in male rats, central injection of antiserum to allopregnanolone significantly potentiated plasma corticosterone response to stress in prepubertal and adult fertile rats as well as in castrated rats. Likewise, in female rats, the stress response of plasma corticosterone was enhanced by passive immunoneutralization of allopregnanolone in prepubertal and fertile rats throughout the estrous cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Alteration in circadian rhythm of plasma corticosterone in rats following sociopsychological stress induced by communication box

The purpose of present study was to investigate the physiological characteristics of sociopsychological stress induced by the communication box method. In this method, the nonfoot shocked rats were used as the psychological stressed experimental group. The stress exposure was loaded for 1 h between 0900 and 1000, daily. The changes in circadian rhythm of plasma corticosterone were studied following the 3-day, 5-day, or 10-day stress exposure, respectively. Plasma corticosterone levels of foot shocked rats and nonfoot shocked rats following the 3-day or 5-day stress exposure were significantly higher than those of control rats. Particularly, the marked elevation of plasma corticosterone was observed at the peak time of circadian rhythm (2100) in the both stress groups. Consequently, the amplitude of 24 h rhythm increased significantly, but the acrophase was not changed. However, the changes of plasma corticosterone levels of both stress groups following the 10-day stress exposure approached those of control group. These results suggest that the repeated exposure of sociopsychological stress can influence the circadian rhythm of plasma corticosterone. The communication box method may be a valuable tool for researching the etiology of human psychiatric disorders with rhythm disturbance.

Adrenal activity in the female lizard Lacerta vivipara jacquin associated with breeding activities

Variations of adrenal activity were studied in captive viviparous females Lacerta vivipara, in relation to breeding activities. The study was restricted to the period of active life which includes both the phase of annual reproduction and a phase of sexual inactivity. Significant seasonal changes in plasma corticosterone levels were measured with a peak during the second half of gestation followed by an abrupt fall at parturition. No significant variations in plasma aldosterone levels were observed. A limited extraovarian production of progesterone was detected which might be of adrenal origin. The half-life of injected tritiated corticosterone was not longer in pregnant than in nonreproductive females, suggesting that the peak of circulating corticosterone in pregnant females corresponds to an increase in the production rate of the hormone. The functional importance of the pituitary-adrenal axis was demonstrated in vivo: plasma corticosteroid levels dropped to the detection limit after adenohypophysectomy. Seasonal variations of adrenal sensitivity to synthetic ACTH 1–39 were examined in vitro, using a perifusion system. No significant variations were observed throughout the period of active life. These results suggest that the peak of plasma corticosterone during gestation can be ascribed to activation of the pituitary-adrenal axis. Experimental modifications of circulating corticosterone level during late gestation altered the timing of parturition, thus indicating that the fall of corticosterone just before term may be involved in the process of parturition in the female L. vivipara.

Effects of environmental temperature on hypothermia and neuroendocrine changes induced by soman

The effects of environmental temperature on body temperature and neuroendocrine parameters were evaluated following a single acute dose (60 μg/kg) of soman. Plasma levels of corticosterone, glucose, and free fatty acids, as well as acetylcholinesterase activity in plasma, erythrocytes, and brain were determined over a 96-hr time course in rats maintained at 23–25, 14–16, and 3–5°C. Considerable inhibition of plasma and erythrocyte acetylcholine hydrolysis activity was observed after administration of soman at all three environmental temperatures. The degree of hypothermia in all soman-treated rats in each environment tested was associated with the amount of brain acetylcholinesterase inhibition. In animals maintained at 23–25 and 14–16°C, changes in plasma corticosterone levels were influenced by central acetylcholine hydrolysis. Hyperglycemia was found only in rats with greater than 45% brain inhibition regardless of environmental temperature. However, the plasma concentration of glucose over the 96 hr test period varied in relation to the hydrolysis of acetylcholine in soman-treated rats. Recovery of plasma acetylcholinesterase was more rapid at lower environmental temperatures. A greater inhibition of central acetylcholinesterase was found in soman-treated rats exposed to 3–5°C. Soman may be more toxic at low environmental temperatures.

Splenic immune responses following treadmill exercise in mice.

The in vitro proliferation response to lipopolysaccharide and pokeweek mitogen by splenic lymphocytes and the effect on the total splenic lymphocyte number were examined in C57BL/6J mice following an 8-week treadmill training program (30 m/min, 8 degrees slope, 30 min/day, 5 times/week) and after a single bout of exhaustive exercise (50% stepwise increases in final running speed for 10-min intervals). Plasma corticosterone levels were also measured to evaluate whether changes in adrenocortical activation were associated with exercise-induced immunomodulation. In comparison to sedentary controls, trained mice had an increase of 35% in succinate dehydrogenase activity per unit of protein in the quadriceps femoris muscle. Trained mice showed an increase in splenic lymphocyte proliferation to both mitogens which was evident 72 h after completion of the final training session, relative to sedentary controls. Immediately following exercise, however, lymphocyte proliferative responses were depressed compared with the training and the control values. The exercise regimen resulted in a reduction in total number of mononuclear cells per spleen. Changes in plasma corticosterone levels after exercise were not clearly associated with immunodepression or immunoenhancement of splenic lymphocyte mitogenesis. Taken together, the data suggest that moderate endurance training augments splenic B lymphocyte mitogenesis and further, that the immediate effects of exercise on splenic immune function vary with the duration and intensity of the work.

Genetic differences in plasma corticosterone levels in response to nicotine injection

Changes in plasma corticosterone (CCS) levels following intraperitoneal injections of nicotine were measured in four inbred mouse strains: DBA/2Ibg, C57BL/6Ibg, C3H/2Ibg, and A/J. In all four strains, nicotine produced a dose-dependent (0.5–2.0 mg/kg nicotine) increase in plasma CCS levels which peaked 10–30 min after injection. Saline increased plasma CCS levels in C57BL, A, and C3H, but not in DBA mice. After correcting for plasma CCS levels produced by saline injection, the nicotine-induced rise in plasma CCS was significantly lower for the C57BL strain than for the other three strains tested. These mouse strains also varied in their responses to saline injection with the rank order: C57BL > A = C3H > DBA. However, the two most divergent strains (C57BL and DBA) did not differ in the effects of a cold water stress. The response to nicotine was completely inhibited by mecamylamine in two strains tested (C3H and C57BL) whereas the response to saline injection was unaffected, suggesting that only the response to nicotine was mediated by nicotinic receptors. It is clear that elevations in plasma CCS induced either by saline injection or by nicotine are influenced by genetic factors.

Combined effect of whole‐body vibration and noise on the dopamine turnover in the rat brain

In order to clarify the combined effects of whole‐body vibration and noise on dopamine (DA) metabolism within the brain, which is known to regulate the response of the organism to various stimuli, the DA turnover rate in regions of the rat brain was determined. The rats were divided into five groups: (1) control; (2) wholebody vibration (4 G, 20 Hz, 90 min) exposure alone; (3) noise [70 dB(A), 90 min] exposure alone; (4) noise [100 dB(A), 90 min] exposure alone; and (5) combined exposure for 90 min to whole‐body vibration (4 G, 20 Hz) and noise [100 dB(A)]. Changes of plasma corticosterone levels were examined as indices of the pituitary‐adrenal function (PAF). The whole‐body vibration exposure alone caused increases in the DA turnover rate [an increase of homovanillic acid (HVA) or HVA/DA] in the frontal cortex and nucleus accumbens. Noise exposure alone caused metabolic increases in the amygdala. The combined effect of whole‐body vibration and noise on the DA neuron systems suggested that the response of the PAF to the combined stimulus was greater than that to each stimulus alone.

Further studies on circadian hormone rhythms after local pharmacological destruction of the serotoninergic innervation of the rat suprachiasmatic region before the onset of the corticosterone rhythm

In previous studies we observed that local pharmacological destruction of the serotoninergic innervation of the hypothalamic suprachiasmatic nucleus before the onset of the circadian plasma corticosterone rhythm interferes with the appearance of the corticosterone rhythm up to the age of two months. In the present investigations we studied other hormone rhythms in such rats and tested animals for corticosterone rhythm when they were older than two months. We found normal circadian fluctuations in plasma testosterone and prolactin levels, variations in growth hormone concentrations, but no changes in plasma corticosterone levels of 63-day-old rats receiving 5,7-dihydroxytryptamine, a neurotoxin selectively destroying the serotoninergic structures, into the suprachiasmatic nucleus at the age of 16 days. Rats did show circadian variations in plasma corticosterone concentrations when tested 3 months after treatment with the neurotoxin. In these latter animals, a significant amount of serotonin-immunoreactive fibers and terminals were evident in the suprachiasmatic nucleus. Only a very few of such elements were seen in rats with a shorter postoperative survival. Our data support the view that serotoninergic innervation of the suprachiasmatic nucleus is essential for the onset of the circadian fluctuations of plasma corticosterone concentrations.

Does neophobia necessarily imply fear or anxiety?

Mice which had the opportunity to move around freely in simultaneously presented novel and familiar environments, did not display significant changes in plasma corticosterone levels nor in autonomic responses. In contrast, the signs of anxiety only appeared when mice were unable to regulate their own approach towards novelty, by preventing them from returning to their familiar compartment once they had freely entered the unfamiliar one, or by placing them physically into the novel compartment. These results demonstrate that contrary to the view generally encountered in the literature, anxiety, or fear, is not induced by novelty per se but when animals are artificially confronted novel stimuli and prevented from displaying normal neophobic responses.