Biomedical subjects

V M Wiegant

Publications and source records attributed to V M Wiegant.

At least 73 records · Page 4Linked to original sources

PubMed1996

Distribution of Lys-gamma 2-melanocyte-stimulating hormone- (Lys-gamma 2-MSH)-like immunoreactivity in neuronal elements in the brain and peripheral tissues of the rat.

Using an antiserum raised against Lys- gamma 2-melanocyte-stimulating hormone (Lys- gamma 2-MSH), with a high specificity for this peptide and its des-Lys derivative, gamma 2-MSH, we found Lys- gamma 2-MSH-like immunoreactivity to have a widespread distribution in the rat brain. In colchicine-treated rats, groups of immunopositive cell bodies were found in the intermediate and anterior lobes of the pituitary gland, in the hypothalamic arcuate nucleus and in the commissural part of the nucleus of the solitary tract (NTS). Immunopositive fibers were found to originate from the latter two cell body regions. The distribution of these fibers was similar to that of the pro-opiomelanocortin containing cell bodies and projections as it has been described previously. Immunopositive terminals were found in brain region containing neurons which have been shown to express mRNA for melanocortin receptors, though the distribution of Lys-gamma 2-MSH-like immunoreactivity is considerably more widespread than that of mRNA for the 'gamma-MSH receptor' (the melanocortin MC3 receptor), which has been reported to be mainly expressed in the hypothalamus. In the periphery Lys-gamma 2-MSH immunoreactivity was localized in the adrenal medulla and in neuronal fibers and varicosities in the heart. The vascular system, the bronchi and kidney were immunonegative. The occurrence of Lys-gamma 2-MSH immunoreactivity in many of the brain regions which are involved in cardiovascular regulation offers leads for further studies on the putative role of gamma-MSHs in cardiovascular control. The occurrence in the rat heart of Lys-gamma 2-MSH-containing fibers suggests a role of the gamma-MSHs in cardiac function.

Animals↗

PubMed1996

The premenstrual phase and reactions to aversive events: a study of hormonal influences on emotionality.

Fifty-eight normal cycle, healthy women were confronted with an aversive, anger-provoking situation in the laboratory. Eighteen women were tested in their follicular phase. A further 40 women were tested in the premenstrual phase, half of whom reported suffering from complaints of premenstrual emotional lability and irritation, the other half reported being without premenstrual problems. Apart from a strong effect of emotion induction on cardiovascular arousal and anger-related moods in the follicular and premenstrual groups, a premenstrual phase effect was also demonstrated, with premenstrual women showing evidence of being more affected by the manipulations on systolic blood pressure and intensity of angry behaviour during anger provocation. Furthermore, some differences were found between those subjects who reported suffering from premenstrual complaints and those free of such complaints, among the most interesting ones being differences in cortisol level preceding the experimental session, in intensity of angry behaviour, and in report of anger intensity at debriefing. The study indicates that the premenstrual phase may have the effect of making women more susceptible to responding emotionally to negative life events.

Adult↗

PubMed1996

Alterations of beta-endorphin-like immunoreactivity in CSF following behavioral training using a passive avoidance procedure.

The central opioid system may have an important influence on memory processes. In view of this, the concentration of beta-endorphin-like immunoreactivity (beta-ELIR) in cerebrospinal fluid (CSF) was measured by a radioimmunoassay in rats trained in a passive avoidance procedure. The beta-ELIR in CSF was examined immediately, 2, 5, 10, and 30 min after the learning trial in which rats were exposed to footshock (0, 0.25, or 1.0 mA for 3 s). Avoidance latency and beta-ELIR in CSF were examined 24 and 120 h after the learning trial. The beta-ELIR in CSF was increased at 5 min after the learning trial in rats exposed to footshock of 0.25 mA. The beta-ELIR in CSF was elevated at 5 and 10 min, followed by a significant decrease at 30 min after the learning trial in rats exposed to a footshock of 1.0 mA. Thus, although an increase in beta-ELIR in CSF was not, the duration of the increase was, related to the shock intensity. Interestingly, a decrease followed the increase in beta-ELIR in CSF which was significant only in rats exposed to the high shock intensity. Avoidance latencies were enhanced in a shock intensity-dependent manner at both 24 and 120 h retention tests. No change in beta-ELIR in CSF was found during retention trials. The results suggest that behavioral manipulations alter beta-ELIR in CSF. An increase in beta-ELIR in CSF may be highly associated with stressful and emotional responses during behavioral training.

Animals↗

PubMed1996

Effect of CRH on the preovulatory LH and FSH surge in the cyclic rat: a role for arginine vasopressin?

The effect of intracerebroventricular (i.c.v.) injection or infusion of various doses of corticotropin-releasing hormone (CRH) on the LH and FSH surge was studied in pro-oestrous rats supplied with a jugular vein and an i.c.v. cannula. Additionally, we investigated if arginine vasopressin (AVP) was involved in the CRH-induced alterations to the surge of gonadotropins. I.c.v. injection of 10 micrograms CRH given 5 min before the presumed onset of the LH surge caused a strong inhibition of the LH surge and a slight inhibition of the FSH surge. Three to four h after CRH injection, its inhibitory effect diminished. A 6'h i.c.v. infusion of CRH started 1 h before the presumed onset of the LH surge, caused a dose-related inhibition of the LH and FSH surge. Infusion of 1 micrograms/h CRH did not suppress the surge of both hormones while infusion of 5 or 10 micrograms/h CRH inhibited the LH surge. Infusion of 10 micrograms/h CRH caused a strong suppression of plasma LH during the first 3 h of the LH surge. Despite continuation of CRH infusion, the inhibitory effect disappeared and plasma LH increased to similar levels as in controls at corresponding points of time of the LH surge. The FSH surge was also suppressed by infusion of 10 micrograms/h CRH. The surge of LH and FSH was not affected by a 9-h infusion of 10 micrograms/h CRH started 4 h before the presumed onset of the LH surge. This observation also indicates that the inhibitory effect of CRH may last for only 3-4 h. The surge of LH and FSH was not affected by i.c.v. injections of AVP-antiserum. However, pretreatment with AVP-antiserum prolonged the inhibitory effect of CRH on the LH surge. In conclusion, CRH can inhibit the pro-oestrous LH and to a lesser extent the FSH rise for only 3-4 h after the beginning of CRH administration. AVP may play a role in limiting the inhibitory effect of CRH on LH to 3-4 h.

Animals↗

PubMed1996

Sensitization of the colonic response to novel stress after previous stressful experience.

Stressful life events may be important causative or precipitating factors for functional gastrointestinal disorders such as the irritable bowel syndrome in humans. In the rat, a single session of foot shocks is known to sensitize the behavioral and hormonal responses to subsequent stress, but intestinal responses have not been investigated. Rats were fitted with bipolar electrodes on proximal colon and exposed to a single session of foot shocks (10 x 6 s in 15 min; preshocked) or no shocks (control). Weight gain after foot shocks was identical to that in controls. Two weeks after foot shocks, basal colonic spike burst frequency did not differ from controls or from that recorded before shock treatment. Unlike controls, however, preshocked rats showed a significant increase in colonic spike burst frequency to a novel stressful challenge in the home cage, an electrified prod. Because the behavioral responses to this challenge did not differ, colonic hyperresponsiveness in preshocked rats may represent a form of stress-induced autonomic sensitization. The model should be a useful tool to study mechanisms and pharmacotherapeutic approaches of the gastrointestinal consequences of traumatic stress.

Animals↗

PubMed1995

Ba2+ replaces Ca2+/calmodulin in the activation of protein phosphatases and in exocytosis of all major transmitters.

Exocytosis from nerve terminals is triggered by depolarization-evoked Ca2+ entry, which also activates calmodulin and stimulates protein phosphorylation. Ba2+ is believed to replace Ca2+ in triggering exocytosis without activation of calmodulin and can therefore be used to unravel aspects of presynaptic function. We have analysed the cellular actions of Ba2+ in relation to its effect on transmitter release from isolated nerve terminals. Barium evoked specific release of amino acid transmitters, catecholamines and neuropeptides (EC50 0.2-0.5 mM), similar to K-/Ca(2+)-evoked release both in extent and kinetics. Ba(2+)-and Ca(2+)-evoked release were not additive. In contrast to Ca2+, Ba2+ triggered release which was insensitive to trifluoperizine and hardly stimulated protein phosphorylation. These observations are in accordance with the ability of Ba2+ to replace Ca2+ in exocytosis without activating calmodulin. Nevertheless, calmodulin appears to be essential for regular (Ca(2+)-triggered) exocytosis, given its sensitivity to trifluoperizine. Both Ba(2+)-and Ca(2+)-evoked release were blocked by okadaic acid. Furthermore, anti-calcineurin antibodies decreased Ba(2+)-evoked release. In conclusion, Ba2+ replaces Ca2+/calmodulin in the release of the same transmitter pool. Calmodulin-dependent phosphorylation appears not to be essential for transmitter release. Instead, our data implicate both Ca(2+)-dependent and -independent dephosphorylation in the events prior to neurotransmitter exocytosis.

Animals↗

PubMed1995

Behavioral studies on the putative gamma-type endorphin receptor using different antibodies.

To investigate the significance of endogenous, neuroleptic-like gamma-type endorphins and their putative receptors, polyclonal and monoclonal antibodies against gamma-type endorphins, which may bio-inactivate the ligands for the receptors, and monoclonal anti-idiotype antibodies, which presumably bind to the receptors, were injected into the nucleus accumbens of the rat brain. The desenkephalin-gamma-endorphin-induced antagonism of the hypomotility response elicited by challenge with apomorphine injected into the nucleus accumbens was used as test system. Both the anti-desenkephalin-gamma-endorphin antibodies and anti-idiotype antibodies blocked the action of exogenous desenkephalin-gamma-endorphin. Thus, the anti-idiotype antibodies may serve as receptor antagonists. Chronic treatment (injection into the nucleus accumbens) with the anti-idiotype antibodies induced sustained hypermotility, decreased habituation and impaired passive avoidance behavior. In such treated animals local treatment with apomorphine did not elicit hypomotility. It is suggested that gamma-type endorphins influence the setpoint for feedback regulation in dopaminergic neurons equipped with gamma-type endorphin receptor systems.

Animals↗

PubMed1995

Social play alters regional brain opioid receptor binding in juvenile rats.

An in vivo autoradiographic procedure was employed to visualize local changes in brain opioid receptor occupancy in juvenile rats. This procedure is based on the assumption that released endogenous ligand will exclude exogenously applied tracer, in this case [3H]diprenorphine, from opioid receptors. Increases in availability of opioid peptides will then result in decreased opioid receptor binding. From behavioral studies there is ample evidence that opioid systems are involved in the regulation of social play behavior in juvenile rats. In the present study, changes in regional brain opioid activity as a result of social isolation-induced social play behavior were monitored. Twenty-one-day-old rats were socially isolated for 0, 3.5 or 24 h prior to testing, and tested alone or in a dyadic encounter. After behavioral testing, [3H]diprenorphine was administered and the brain was prepared for autoradiography. Social isolation caused increases in social behavior (dyadic encounters) but not in non-social behavior (singly tested animals). Modest differences in brain opioid receptor binding due to social isolation, social play behavior, or an interaction of the two, were found in claustrum, nucleus accumbens, globus pallidus, paraventricular and arcuate nuclei of the hypothalamus, and the dorsolateral and paratenial thalamic nuclei. These results support the notion that opioid systems are involved in the regulation of social play behavior. In addition, the observation of changes in opioid binding in areas involved in reward processes, adds evidence to the hypothesis that opioid systems are involved in the regulation of the rewarding aspects of social play in juvenile rats.

Animals↗

PubMed1995

Effects of novelty and conditioned fear on small intestinal and colonic motility and behaviour in the rat.

Novelty and conditioned fear were used to investigate the effects of psychological stress on fasting small intestinal and colonic myoelectric activity and their relation with behaviour in freely moving rats fitted with bipolar electrodes on proximal jejunum and colon. Rats in both novelty and conditioned fear groups spent a 15 min session in a novel box, where only rats in the fear group received unescapable, repeated foot shock (10 x 6 s, 0.5 mA). Behaviour in groups reexposed to the box on day 1 or day 7 indicated a profound difference in emotional state. Conditioned fear rats remained largely immobile, while novelty rats displayed active exploratory behaviour. Behaviour during conditioned fear did not differ significantly between rats reexposed to the box either 1 or 7 days after foot shock, while novelty animals appeared more aroused on day 7. Conditioned fear on day 1 caused a significant increase in colonic spike burst frequency compared to basal values in the home cage. A smaller but significant increase was found in novelty rats. In groups tested after 7 days, both novelty and conditioned fear resulted in small increases in colonic burst frequency that did not differ significantly from each other. No effects were found on the incidence of the fasting jejunal Migrating Motility Complex. Defecation was see only in conditioned fear rats, but did not differ quantitatively between day 1 and day 7. We conclude that, in the rat, colonic myoelectric spike burst activity is highly responsive to psychological stress, while the fasting pattern of small intestinal activity is more resistant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

The effect of chronic stress on plasma cortisol concentrations in cyclic female pigs depends on the time of day.

The influence of tethered housing (a condition of chronic stress) on morning and evening basal plasma cortisol levels was investigated in a longitudinal study in cyclic female nulliparous pigs (gilts). After a period of loose housing in individual pens ("nonstress" estrous cycles), six cannulated gilts were tethered by a neck chain and housed for a period of 20 wk (chronic stress estrous cycles). Blood was sampled twice daily (1000 and 1800 hr) for cortisol determination. Plasma cortisol levels showed a diurnal rhythm with significantly higher levels at 1000 hr than at 1800 hr. Tethered housing induced a significant increase in the 1800-hr plasma cortisol concentrations during the first three estrous cycles after tethering, whereas the 1000-hr plasma cortisol concentrations did not change throughout the experimental period. During the period of increased 1800-hr levels, cortisol was still released in a circadian fashion, albeit, the rhythm was flattened. In control gilts, housed loose during the entire experimental period, plasma cortisol concentrations at 1000 hr and at 1800 hr remained unaltered and 1000-hr cortisol concentrations were significantly higher than the 1800-hr concentrations during the experimental period. Therefore, possible effects of the experimental procedure or age-related effects could be excluded. These data indicate that, in tethered gilts, the chronic stress-induced hypercortisolemia is of transient nature, suggesting adaptive changes in the regulation of the hypothalamic-pituitary-adrenocortical axis. In addition, the data reveal circadian differences in the effect of chronic stress on hypothalamic-pituitary- adrenocortical function.

Animals↗

PubMed1995

Social isolation and social interaction alter regional brain opioid receptor binding in rats.

Endogenous opioid systems have been implicated in the consequences of social isolation and in the regulation of social behavior, although their precise role is not clear. There is not much information on a possible locus in the brain at which opioids exert their effects on social behavior. In an effort to address this issue we analyzed regional opioidergic activity upon social isolation-induced social interaction using in vivo autoradiography. Animals were either socially isolated for 7 days or group housed, and tested singly or in a dyadic encounter. Subsequently, a tracer dose of [3H]diprenorphine was administered and in vivo autoradiographic analysis was performed. Seven days of social isolation caused changes in both social behavior (dyadic encounters) and non-social behavior (singly tested animals). Opioid receptor binding was increased in the medial prefrontal cortex and the parafascicular area in isolates, suggesting that social isolation may evoke an upregulation of opioid receptors in these areas. Social interaction increased opioid binding in the parafascicular area of non-isolated rats. In substantia nigra para compacta and ventral tegmental area binding was increased upon social isolation, and social interaction decreased opioid binding in isolates, but these changes failed to reach significance. These observed local changes in opioid receptor binding suggest a role for opioid systems in discrete areas in the consequences of social isolation and the regulation of social behavior in rats.

Animals↗

PubMed1995

Computer analysis of the migrating motility complex of the small intestine recorded in freely moving rats.

Myoelectric activity of the small intestine was recorded digitally in fasted, freely moving rats fitted with multiple pairs of electrodes in the antimesenterial smooth muscle. The electrodes were implanted under strict aseptic conditions to safeguard the animal's health and thereby benefit experimental results. As in many other mammalian species, the fasted electrical and mechanical activity of the small intestine in the rat consists of alternating periods of activity and quiescence jointly called the Migrating Motility Complex (MMC). Existing methods for the analysis of small bowel myoelectric activity either integrate spike activity over longer periods of time or describe characteristics of single bursts. We have developed a computer program for fast, automated analysis that distinguishes the three characteristic phases of the MMC. The computer program recognizes periods of varying spike burst frequency and then produces a graphical and numerical output of the length and mean burst frequency of the different phases of each MMC that correlates well with the results of visual evaluation. The techniques used are discussed in relation to existing recording and analysis methods, and specific decisions in the program are motivated. The system will be a useful tool in assessing the effects of drugs, peptides, or stress on small bowel motility.

Animals↗

PubMed1995

Chronic stress increases the opioid-mediated inhibition of the pituitary-adrenocortical response to acute stress in pigs.

The role of endogenous opioid mechanisms in the pituitary-adrenocortical response to acute stress was investigated in a longitudinal study in cyclic female pigs before and after exposure to chronic stress (long term tethered housing). Challenge of loose-housed pigs with acute nose-sling stress for 15 min induced an activation of the hypothalamic-pituitary-adrenocortical axis, evidenced by a transient increase in plasma ACTH (peak height above basal, 98 +/- 12 pg/ml; mean +/- SEM) and cortisol (54 +/- 3 ng/ml) concentrations. Pretreatment with the opioid receptor antagonist naloxone (0.5 mg/kg BW, iv bolus) increased the challenge-induced ACTH and cortisol responses to 244 +/- 36 pg/ml and 65 +/- 5 ng/ml, respectively. This indicates that during acute nose-sling stress, endogenous opioid systems are activated that inhibit the pituitary-adrenocortical response. After exposure of the pigs to chronic stress (10-11 weeks of tethered housing), the challenge-induced ACTH response was attenuated, whereas the cortisol response remained unchanged, suggesting an increased adrenocortical sensitivity to circulating ACTH. In addition, pretreatment with naloxone induced a greater increment in the ACTH and cortisol responses in tethered pigs than in loose-housed pigs. As no such changes were found in control animals housed loose during the entire experimental period, this indicates that the impact of opioid systems had increased due to chronic stress. The increased impact of opioid systems during chronic stress may prevent excessive hypothalamic-pituitary-adrenocortical responses to acute stressors and, thus, may be of adaptive value.

Adrenal Cortex↗

PubMed1995

Chronic stress and pituitary-adrenocortical responses to corticotropin-releasing hormone and vasopressin in female pigs.

Effects of long-term tethered housing (a condition of chronic stress) on pituitary-adrenocortical responsiveness to exogenous corticotropin-releasing hormone (CRH) and lysine8-vasopressin (LVP) were investigated in female pigs. Intravenous administration of CRH (dose range 10-440 pmol/kg body wt) or LVP (10-880 pmol/kg body wt) elicited transient and dose-related increases in plasma concentrations of adrenocorticotropic hormone (ACTH) and cortisol. Comparison of the responses induced by the peptides indicated that CRH is a more potent ACTH secretagogue than LVP. Treatment with LVP produced a fivefold greater plasma cortisol/ACTH ratio than treatment with CRH, suggesting that in addition to stimulating pituitary ACTH release it enhanced the ability of the adrenal cortex to secrete cortisol in response to ACTH. Whereas concomitant administration of 10 pmol CRH/kg body wt and 20 pmol LVP/kg body wt revealed an additive effect on ACTH release, synergism between both peptides was found with respect to their cortisol-releasing effect. Ten to thirteen weeks of chronic stress did not alter significantly the absolute ACTH and cortisol responses to the two peptides. In tethered pigs, the cortisol/ACTH ratio after CRH treatment, calculated from the area under the curve, was twofold that in loose-housed pigs. From these observations we conclude that after chronic stress the sensitivity of the adrenocortex to circulating ACTH was increased, whereas the sensitivity of the pituitary to CRH and/or LVP remained unaltered.

Adrenocorticotropic Hormone↗

PubMed1995

Effect of restraint stress on the preovulatory luteinizing hormone profile and ovulation in the rat.

Plasma profiles of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were measured during restraint stress on the day of pro-oestrus; these profiles were considered in relation to ovulation rate on the next day. Rats bearing a permanent jugular vein cannula were subjected to restraint, which was started 0, 1 or 2 h before the presumed onset of the LH surge and ended just before the beginning of the dark period. Exposure to restraint resulted in a suppression of the secretion of both gonadotrophins on the day of pro-oestrus. Suppression of the LH surge was virtually complete (plasma LH < or = 0.2 ng/ml) in 15 out of 32 stressed rats, and the ovaries of these rats contained graafian follicles with oocytes in germinal vesicle stage. In these rats, the LH surge did not occur 24 h later. In the remaining 17 rats, restraint resulted in a considerable suppression of the LH surge. Of these rats, five had an ovulation rate of 100% and four ovulated partially. In unruptured follicles of the latter, the oocyte had not resumed meiosis and the follicle wall was not luteinized. In the remaining eight rats with a reduced LH surge, ovulations had not occurred and graafian follicles were unaffected. The results of this study indicate that during pro-oestrus restraint stress suppresses and does not delay the release of preovulatory gonadotrophins. Partial suppression of LH by restraint does not result in induction of meiotic resumption without subsequent ovulation or in luteinized unruptured follicles.

Animals↗

PubMed1994

Pharmacokinetics of DGAVP in plasma following intranasal and oral administration to healthy subjects.

A pharmacokinetic study was carried out to assess the bioavailability of desglycinamide-[Arg8]vasopressin (DGAVP, Org 5667). DGAVP (2 mg) was administered both intranasally and orally to healthy subjects with a treatment interval of 1 week. Blood samples were taken regularly between 15 min before and 210 min after administration and were assayed for DGAVP by radioimmunoassay. In all subjects endogenous vasopressin (AVP) levels were detectable. Peak levels of DGAVP occurred at 15 min after both treatments. The mean absorption half-life was 8.7 and 7.3 min and the mean elimination half-life was 38 and 34.6 min for the intranasal and oral route of administration, respectively. The bioavailability of orally administered DGAVP was low compared with the intranasally administered drug; the relative bioavailability of oral/nasal administration was 0.7%. The results indicate that DGAVP is absorbed rapidly after both oral and intranasal administration, but the intranasal route of administration of DGAVP is 100 times more effective in increasing plasma DGAVP levels.

Administration, Intranasal↗

PubMed1994

Preferential induction of c-fos immunoreactivity in vasoactive intestinal polypeptide-innervated gonadotropin-releasing hormone neurons during a steroid-induced luteinizing hormone surge in the female rat.

In small rodents, reproduction is critically dependent on the integrity of the circadian oscillator of the brain, the suprachiasmatic nucleus (SCN). Lesions of the SCN induce persistent estrus (anovulation) in intact female rats, whereas estrogen implantation in ovariectomized rats results in daily LH surges, which disappear after SCN lesions. Vasoactive intestinal polypeptide (VIP), a peptide synthesized in cell bodies of the SCN, has been implicated in the regulation of LH release. Recently, we have provided immunocytochemical evidence for a VIP-containing neuronal projection from the SCN to the GnRH system. This suggests that VIP from the SCN may modulate LH release via a direct influence on GnRH neurons. To investigate the involvement of VIP input on GnRH neurons and SCN neurons in the generation of a LH surge, we used immunoreactive c-fos as a marker for cell activation in ovariectomized mature rats and immature rats treated with steroids. VIP-containing fibers were observed in apposition to a substantial portion of the GnRH neurons containing c-fos. Expression of c-fos was more frequently observed in VIP-innervated GnRH neurons than in GnRH neurons in general. This difference in activation was most pronounced during the onset of the LH surge. In SCN neurons, steroid treatment did not induce c-fos immunoreactivity before or during the LH surge. The present results indicate that VIP-containing fibers, possibly originating in the SCN, are involved in the initiation of the LH surge. In view of the reported inhibitory effects of VIP on LH release, it is suggested that the role of VIP input in this respect is permissive.

Animals↗

PubMed1994

Increased cortisol response to exogenous adrenocorticotropic hormone in chronically stressed pigs: influence of housing conditions.

In a longitudinal experiment, the influence of tethered housing (a condition of chronic stress) on the reactivity of the adrenal cortex to exogenous ACTH was investigated in gilts. To that end, the plasma cortisol response to synthetic ACTH (1-24; 10 micrograms/kg of BW; i.v. bolus injection via a permanent catheter) was determined before and after prolonged tethered housing. Two systems for tethered housing were used, one more restrictive than the other with regard to possibilities for visual and tactile contacts with conspecifics and visual control over the environment. The ACTH treatment induced a marked, transient plasma cortisol response in all gilts studied, irrespective of their housing conditions. Long-term tethered housing increased the ACTH-induced cortisol response. Possible effects of the experimental procedure or age-related effects could be excluded, because in control gilts, which were housed loose during the entire experimental period, the cortisol response to ACTH remained unaltered. The chronic stress-induced increase in the ACTH-induced cortisol response was considerably more pronounced and persistent in gilts that were deprived of possibilities for social contacts with conspecifics and visual control over the environment than in gilts with such possibilities. These data indicate that in tethered gilts adaptational changes occur at the level of the adrenal cortex that affect the ACTH-induced adrenocortical response. In addition, not only physical restraint but also restriction of social contact and visual control play an important role in the development of these changes.

Adaptation, Physiological↗