scispace - formally typeset
Search or ask a question

Showing papers on "Pinealectomy published in 1986"


Journal ArticleDOI
TL;DR: The data suggest that the behavioral effects of melatonin, like those on reproduction in seasonally breeding mammals, depend upon an intact circadian system and the SCN.

233 citations


Journal Article
TL;DR: Rats whose circadian rhythms are disrupted or arrhythmic in constant light are synchronized by daily melatonin injection, and the rate and direction of responses to phase-shift of the zeitgeber can be altered with dailyMelatonin administration, suggesting melatonin may be useful therapeutically for such human desynchronizations as jet-lag and shiftwork.
Abstract: While pinealectomy (Px) has little effect on mammalian circadian rhythms, daily injections of the pineal hormone melatonin in rats have profound effects. These can be classified according to their effects under three categories of desynchronization: external desynchronization, internal desynchronization and phase-shift of the zeitgeber (Aschoff, 1969). Externally desynchronized rats, free-running in constant darkness (DD), can be entrained to a 24-hour regime of melatonin injection. Entrainment depends upon the suprachiasmatic nuclei (SCN) since lesions to the SCN prevent it. Although no animal model for internal desynchronization exists, rats whose circadian rhythms are disrupted or arrhythmic in constant light (LL) are synchronized by daily melatonin injection, and the rate and direction of responses to phase-shift of the zeitgeber can be altered with daily melatonin administration. These and other results suggest melatonin may be useful therapeutically for such human desynchronizations as jet-lag and shiftwork, and preliminary data using human subjects are presented.

133 citations


Journal ArticleDOI
TL;DR: A link between pineal function, melatonin secretion and GABA receptor activity in rats is suggested, and melatonin activity on GABA binding did not depend upon a direct effect on the binding sites, as shown in vitro.
Abstract: In order to assess the effect of pinealectomy (Px) on the diurnal rhythmicity of gamma-aminobutyric acid (GABA) high affinity binding to cerebral cortex membranes, groups of intact, Px or sham Px rats (subjected to surgery 15 days earlier) were killed at six different time intervals during the 24-hour cycle. GABA binding was estimated by Scatchard analysis of 3H-GABA binding to cerebral cortex membranes prepared from individual brains; only one type of binding site with dissociation constant (KD) about 20-50 nM and site number (Bmax) about 200-500 fmol/mg protein was apparent in the assay conditions employed. In intact and sham Px rats Bmax attained minimal values at night and increased during daylight. Px increased generally Bmax and disrupted its normal diurnal rhythmicity, a peak in Bmax being observed at midnight. A significant decrease of GABA high affinity binding affinity was detected at morning hours in intact rats and at late scotophase and morning hours in Px and sham Px rats. Bmax of GABA high affinity binding in Px rats attained maximal values by 5-10 days after surgery and decreased somewhat 5 days later. Sham Px rats exhibited a transient increase in Bmax up to 10 days after surgery, returning to normal values by the 15th day. Superior cervical ganglionectomy increased binding affinity up to 15 days after surgery without affecting Bmax. The minimal melatonin effective dose to counteract Px-induced increase of GABA high affinity binding was 25 micrograms/kg body weight when given 3 h before sacrifice. Melatonin activity on GABA binding did not depend upon a direct effect on the binding sites, as shown in vitro. These results suggest a link between pineal function, melatonin secretion and GABA receptor activity in rats.

100 citations


Journal ArticleDOI
TL;DR: Results support a link between pineal activity and brain BZP receptors in rats and support the idea that pineal removal blunted the nocturnal peak of receptor concentration and caused a significant depression of binding site number at noon.
Abstract: In a previous work, pinealectomy was found to depress benzodiazepine (BZP) receptor binding in cerebral cortex membranes of rats killed at noon. In order to assess the effect of pineal removal on diurnal variations of BZP binding site concentration and affinity, groups of intact, pinealectomized, or sham-pinealectomized rats (subjected to surgery 2 wk earlier) were killed at six different time intervals during the 24-h cycle. BZP binding was assessed by Scatchard analysis of 3H-flunitrazepam high-affinity binding to cerebral cortex membranes. In intact and sham-pinealectomized rats, a maximum in BZP receptor concentration was found at midnight. Pinealectomy blunted the nocturnal peak of receptor concentration and caused a significant depression of binding site number at noon. No changes in the affinity of the binding sites for the radioligand were detected as a function of time of day or following surgery. In a dose-response experiment for melatonin ability to restore the depressed BZP receptor concentration of cerebral cortex membranes of pinealectomized rats killed at noon, a minimal effective dose of 25 micrograms/kg body weight was obtained. These results further support a link between pineal activity and brain BZP receptors in rats.

86 citations


Journal Article
TL;DR: In all hamster species investigated, the pineal gland and its hormone melatonin constitute part of the central mechanism whereby environmental information is transduced to neuroendocrine signals responsible for the functional integrity of the reproductive system.
Abstract: In this article we review the functions of the pineal gland and of pineal melatonin in regulating gonadal activity in three species of hamster, the golden (Syrian) hamster (Mesocricetus auratus), the Turkish (Brandt's) hamster (Mesocricetus brandti), and the Djungarian (Siberian, or hairy-footed) hamster (Phodopus sungorus sungorus). Some experimental treatments elicit the same response in all three species; this is especially true for the regulation of the nocturnal elevation of pineal melatonin content and release and for the gonadal response to timed melatonin injections in intact animals throughout the day. In other experimental paradigms, species differences are paramount; pinealectomy or subcutaneous implants of melatonin in intact individuals have different effects on the photoperiodic gonadal response in all species. Yet in all hamster species investigated, the pineal gland and its hormone melatonin constitute part of the central mechanism whereby environmental information (photoperiod) is transduced to neuroendocrine signals responsible for the functional integrity of the reproductive system.

85 citations


Journal Article
TL;DR: Development of assays for urinary melatonin metabolites has made possible the longterm study of circadian variations in different environments and it remains to be seen whether, in physiological amounts, it is causally related to aspects of human sleep and other circadian or seasonal rhythms.
Abstract: The pineal gland, via its hormone melatonin, is of major importance in the transduction of photoperiodic information in animals. It is concerned both with the synchronisation of annual cycles in photoperiodic mammals and with regulation of circadian rhythmicity in lower vertebrates. Its role, if any, in mammalian circadian systems is still speculative. By analogy with animal work the function of the human pineal is most likely to be concerned with seasonal and circadian rhythms. The study of human pineal function depends heavily on the measurement of melatonin in plasma or urine. Radioimmunoassay (RIA) and gaschromatography-mass-spectrometry (GCMS) have been successfully employed to establish the basic 24-hour rhythm. GCMS has also served to validate RIA. Following early work the reported human plasma levels of melatonin have stabilized approximately at less than 20 pg/ml in daytime with mean night time levels around 40-80 pg/ml. The high sensitivity of GCMS measures daytime levels of 2-5 pg/ml. With confidence established in melatonin assays, its physiological and pathological variations can be investigated in full. Development of assays for urinary melatonin metabolites has made possible the longterm study of circadian variations in different environments. The rhythm of melatonin production can be dissociated from the sleep wake cycle in environmental isolation and behaves like a "strong" oscillator variable. In the unusual social and photoperiodic conditions of Antarctica it remains strongly entrained to the 24 hour day. Whilst measurement of melatonin can provide circumstantial evidence of its function, abolition of its production and its administration in humans can uncover causal relationships. The effects of abolition of the melatonin rhythm by beta-adrenergic antagonists or pinealectomy has not yet been extensively studied in man. Melatonin administration, always (to date), in pharmacological amounts has hypnotic effects in man and may, in some individuals modify the rhythmic characteristics of its own secretion. It remains to be seen whether, in physiological amounts, it is causally related to aspects of human sleep and other circadian or seasonal rhythms.

44 citations


Journal ArticleDOI
TL;DR: The usual nocturnal surge of pineal melatonin content was blocked by bilateral superior cervical ganglionectomy and pinealectomy in male Syrian hamsters, which appears to depend on the pineal gland and its sympathetic innervation.
Abstract: The usual nocturnal surge of pineal melatonin content was blocked by bilateral superior cervical ganglionectomy in male Syrian hamsters. Ganglionectomy and pinealectomy each prevented the nocturnal rise of serum melatonin concentration seen in control animals. The normal nocturnal surge of circulating melatonin in this species appears to depend on the pineal gland and its sympathetic innervation.

38 citations


Journal ArticleDOI
TL;DR: Adult male Turkish hamsters maintained testicular function when exposed to photoperiods of 15, 16, or 17 h of light per day, and animals exposed to 14-18 and 20 h ofLight per day had a robust nocturnal melatonin rhythm.
Abstract: Adult male Turkish hamsters maintained testicular function when exposed to photoperiods of 15, 16, or 17 h of light per day. Photoperiods of less than 15 or greater than 17 h of light per day induced a rapid and complete testicular regression. As pinealectomy had been shown by others to induce testicular regression in longday Turkish hamsters, we thought that regression on 18 or more h of light might be based on the inability of the pineal to generate a daily rhythm of melatonin in production and release. This proved not to be the case. Animals exposed to 14-18 and 20 h of light per day had a robust nocturnal melatonin rhythm.

38 citations


01 Jan 1986
TL;DR: It is indicated that the pineal organ in catfish is involved in the regulation of locomotor activity rhythms and in some aspects of osmoregulation and Circadian rhythms in plasma cortisol, osmolality and electrolytes, but there were no significant differences in the mesor values of plasma cortisol.
Abstract: The findings reported here indicate that the pineal organ in catfish is involved in the regulation of locomotor activity rhythms and in some aspects of osmoregulation. Under LD 12:12 regimen, catfish is nocturnally active, with the maximum activity just before dawn. However, under conditions of continuous darkness (DD), the locomotor rhythm became free-running. Pinealectomy abolished the activity rhythm under DD and resulted in arrhythmicity. Circadian rhythms in plasma cortisol, osmolality and electrolytes (Na+ and K+) were also observed. Pinealectomy, though, increased the amplitudes of the rhythm; however the differences were not statistically significant. Removal of pineal significantly increased the mesor values of plasma osmolality and electrolytes, but there were no significant differences in the mesor values of plasma cortisol.

37 citations


Journal ArticleDOI
TL;DR: There was no synchronous periodic kemp activity: some follicles remained active at all times, and the seasonal pattern of plasma prolactin levels disappeared, but the relationship between the kemp follicle cycle and the pattern of Plasma Prolactin concentrations and its control by the pineal gland are discussed.
Abstract: Twelve adult Limousine rams (five pinealectomized, four sham operated, and three control) were housed under an artificial lighting regime of alternating periods of long (16L:8D) and short (8L:16D) days for 18 months, and long-term variations in kemp follicle growth were recorded along with measurements of the plasma prolactin concentrations. In control and sham-operated rams, both parameters varied in relation to imposed lighting regime. Moult and growth of the kemp follicles occurred during each short-day period at a time when the concentrations of prolactin were low and vice versa. Variations in the pinealectomized rams were different from those in the control or sham-operated ones. There was no synchronous periodic kemp activity: some follicles remained active at all times, and the seasonal pattern of plasma prolactin levels disappeared. The relationship between the kemp follicle cycle and the pattern of plasma prolactin concentrations and its control by the pineal gland are discussed.

34 citations


Journal ArticleDOI
TL;DR: While pinealectomy completely prevented the inhibitory effects of blinding on PRL synthesis in males, it was less effective in female hamsters inasmuch asPRL synthesis was still nearly 50% lower in blind pinealectomized animals than in controls.
Abstract: In order to determine the role of the pineal gland in mediating the effects of long-term light deprivation on prolactin (PRL) cell activity in a highly photosensitive species, PRL synthesis, storage a

Journal ArticleDOI
TL;DR: The findings suggest that the pineal gland plays no major role in mediating the onset of the inhibition of LH and FSH secretion that occurs during transition from the infantile to the prepubertal phase of development and, therefore, is not responsible for initiating the protracted delay in the advent of puberty in this higher primate.
Abstract: The present study was undertaken to determine whether pineal hormones are responsible for initiation of the prepubertal hiatus in gonadotropin secretion that is observed between 2–3 months of age in the infantile male rhesus monkey. Six neonatally orchidectomized rhesus monkeys were pinealec-tomized at 4–6 weeks of age using a microneurosurgical technique. The time courses of circulating LH and FSH concentrations during the first 36 weeks of life in these animals were determined in weekly samples by RIA and compared to those observed in sham pinealectomized animals (n = 2) and in ago-nadal infantile males with an intact central nervous system (n = 3). The completeness of pinealectomy was verified by an absence of pineal rests in serial coronal sections of the brain. The absence of nocturnal elevations in circulating immunoreactive melatonin concentrations in pinealectomized monkeys was consistent with the foregoing histological findings. The developmental pattern of gonadotropin secretion in pinealectomiz...


Journal ArticleDOI
TL;DR: Subcutaneous implantation of melatonin for a period of 12 weeks with reinforcement of implants every fortnight had no significant influence on photoinduced gonadal development in the pigeon.
Abstract: Subcutaneous implantation of melatonin for a period of 12 weeks with reinforcement of implants every fortnight had no significant influence on photoinduced gonadal development in the pigeon. Neither the weight of the gonads or the oviduct nor the gonadal size was affected by melatonin. Pinealectomy also was found to have no significant influence on gonadal weight when examined 20 weeks after the surgery. The plasma levels of luteinizing hormone and testosterone were not significantly influenced by a 10-week implantation of melatonin, although a trend toward an increase (statistically insignificant) in testosterone concentration was apparent in melatonin-implanted male pigeons. Plasma concentration of estradiol was found to increase significantly in both male and female pigeons following the 10-week melatonin implantation. A trend toward an increase in plasma corticosterone level was also apparent in these melatonin-implanted birds, but the increase was statistically insignificant.

Journal Article
TL;DR: A series of cases are presented to illustrate various facets of the clinical management of pineal tumors, with emphasis on markers of normal and neoplastic pineal function, and in particular melatonin.
Abstract: A series of cases are presented to illustrate various facets of the clinical management of pineal tumors. Emphasis is placed on markers of normal and neoplastic pineal function, and in particular melatonin. Although variable before therapy, after therapy four of five patients had little evidence of melatonin production, suggesting that pinealectomy had been complete.

Journal ArticleDOI
TL;DR: Results demonstrate an inhibitory pineal influence on adrenal DBH activity, and that this was dose dependent, and the inhibitory effect of exogenous melatonin on adrenomedullaryDBH activity depended upon the presence of the pineal, suggesting a mediating role of the Pineal in this particular action of melatonin.
Abstract: Pineal influence in the control of adrenomedullary function in golden hamsters was investigated by examining changes in adrenal dopamine-beta-hydroxylase (DBH) activity following pinealectomy, either alone or in combination with melatonin administration. Adult males acclimated to an LD 14:10 photoperiod were distributed in five experimental groups: intact controls (NO), sham-pinealectomized (S), sham-pinealectomized with black plastic shielding of the pineal region, pinealectomized (PX), and pinealectomized with the operated region shielded. Animals representing all of these groups were injected (between L11 and L11.75) with either vehicle, or a low dose (25 micrograms) or a high dose (2,500 micrograms) of melatonin daily for 28 days, after which they were killed, and the adrenals were collected for assay of DBH activity by means of a sensitive radioenzymatic method. We found that PX + vehicle led to increased (P less than .05) adrenal DBH activity in comparison with either NO or S groups; daily 25 micrograms of melatonin resulted in lowered DBH activity in the NO group when compared with NO + vehicle (P less than .001) or S + vehicle (P less than .001) groups; PX + 25 micrograms melatonin reversed the action of 25 micrograms melatonin in the NO + 25 micrograms group; 2,500 micrograms melatonin was without effect on adrenal DBH in any of the injected surgical groups. These results show an inhibitory pineal influence on adrenal DBH activity, and that this was dose dependent.(ABSTRACT TRUNCATED AT 250 WORDS)

Journal ArticleDOI
TL;DR: It is suggested that melatonin differentially inhibits FSH and LH secretion from isolated superfused hamster anterior pituitaries, with a return to baseline levels only upon melatonin withdrawal.

Journal ArticleDOI
TL;DR: The effects of photoperiod or pinealectomy were not evident for any of the dependent measures during pregnancy, and the role of the pineal gland in mediating short-day effects is discussed.
Abstract: Food intake, food retrieval, and body weight changes were measured in female Syrian hamsters maintained under long and short photoperiods, and in animals sustaining pinealectomy or sham surgery Animals maintained under short photoperiods gained more weight, ingested more food, and brought more food from more distant compartments into their nest compart ments than did animals maintained under long photoperiods Pinealectomy prevented the short- day elevations in body weight and food retrieval during the period of gonadal recrudescence, but it did not produce significant changes during the period of gonadal regression; in contrast, pinealectomy prevented the short-day increases in food intake only during initial weeks of the period of gonadal regression: The effects of photoperiod or pinealectomy were not evident for any of the dependent measures during pregnancy The role of the pineal gland in mediating short-day effects is discussed

Journal ArticleDOI
TL;DR: The data do not support the assumption of the important role of the pineal in the newborn rat for the maintenance of a normal circadian rhythm of the pituitary-adrenal system.
Abstract: Newborn male and female rats aged between 24 and 48 hours were pinealectomized (Px) or sham-operated (Sh). Animals were sacrificed at 45 and 60 days of age, at the trough and peak of the adrenocortical diurnal cycle. Blood was collected for corticosterone determinations and the adrenal glands weighed. Adrenal gland weight was greater at 45 days (p<0.01) in Px rats than in Sh rats. This difference in adrenal gland weight disappeared in the group sacrificed 60 days post-operatively. On the other hand, the diurnal plasma rhythm of corticosterone remained intact in male and female rats with or without pineal at 45 and 60 days. Furthermore, the trough and peak plasma corticosterone levels were not different in Px 45 and 60 days post-operatively. These data do not support the assumption of the important role of the pineal in the newborn rat for the maintenance of a normal circadian rhythm of the pituitary-adrenal system.

Journal Article
01 Jan 1986-Cytobios
TL;DR: The effects of pinealectomy on the mitotic activity of regenerating adrenal cortex of rats were studied on the second, seventh and twelfth days following the enucleation of adrenals.
Abstract: There is some evidence that the pineal gland may influence the proliferation of both normal and neoplastic cells. The adrenal cortex has very high capacity for regeneration. Therefore, the effects of pinealectomy on the mitotic activity of regenerating adrenal cortex of rats were studied on the second, seventh and twelfth days following the enucleation of adrenals. Pinealectomy caused a significant decrease in the mitotic index of regenerating adrenal cortex after 2 and 12 days in comparison to sham operated controls.

Journal ArticleDOI
TL;DR: Seasonal alterations and the effect of pinealectomy on carbohydrate metabolism as revealed by tissue glycogen content and blood glucose levels of normal, sham operated and pinealectomised domestic pigeons, Columba livia (Gmelin), have been studied.
Abstract: SUMMARY Seasonal alterations and the effect of pinealectomy on carbohydrate metabolism as revealed by tissue glycogen content and blood glucose levels of normal, sham operated and pinealectomised domestic pigeons, Columba livia (Gmelin), have been studied. Pinealectomy performed during the breeding season induced increased hepatic and gonadal glycogen contents and a reduced glycemic level, changes characteristic of intact birds during the nonbreeding season. In contrast, pinealectomy performed during the nonbreeding season induced decrement in the glycogen content of the liver and gonads and an increase in blood glucose level, changes characteristic of intact birds during the breeding season. The phase shift in carbohydrate metabolism noted to occur in response to pinealectomy is discussed in terms of the phase shift in gonadal activation induced by pinealectomy.

Journal ArticleDOI
TL;DR: Pinealectomy in the nonbreeding phase appeared to hasten the process and degree of gonadal regression occurring in the intact birds, indicating the progonadal role of the pineal in tropical wild pigeons.
Abstract: SUMMARY Seasonal and pinealectomy induced changes in weight and histological profile of the gonads have been studied during the recrudescent, breeding and regression phases of the feral pigeons, Columba livia (Gmelin). Whereas the intact birds showed enlarged active gonads during the recrudescent and breeding periods, the pinealectomised birds depicted involuted gonads with germ cell degeneration in the seminiferous tubules of testis and arrested folliculogenesis with marked atresia in the ovary. The reduction in weight induced by pinealectomy during these periods ranged from 60 to 70%. The histological appearance of the gonads of pinealectomised birds was markedly more regressed than the normally regressing gonads of intact birds during the nonbreeding phase. Pinealectomy in the nonbreeding phase appeared to hasten the process and degree of gonadal regression occurring in the intact birds. These observations are taken to indicate the progonadal role of the pineal in tropical wild pigeons and this is disc...

Journal ArticleDOI
TL;DR: Presynaptic mechanisms such as synthesis and storage of both NE and DA appear to have little, if any, effect on pinealectomy‐induced convulsions, whereas enhancing synaptic levels of NE by blocking its reuptake into adrenergic axons had an anticonvulsant effect.
Abstract: Removal of the pineal gland produces stereotyped tonic convulsions in parathyroidectomized rats. Inasmuch as central levels of norepinephrine (NE) are decreased in these animals, the purpose of this study was to investigate the effects of alterations in central catecholamine function on convulsions produced by pinealectomy in parathyroidectomized rats. The treatment of rats with alpha-methyl-p-tyrosine or FLA-63 produced large reductions in forebrain levels of both NE and dopamine or NE alone, respectively, which were not associated with facilitation of convulsions. However, the incidence of convulsions was increased by FLA-63 in rats pretreated with the catecholamine precursor L-dihydroxyphenylalanine. Reserpine, a monoamine depleter, had no effect on either the incidence or severity of convulsions. An acute injection of desipramine, an inhibitor of the reuptake of NE, however, significantly lowered the incidence of convulsions. Timolol, a beta-adrenergic receptor antagonist, reduced, in a dose-dependent manner, the average latency to onset of convulsions and increased the average number of convulsions each rat experienced. Clonidine, an alpha 2-adrenergic agonist, did not significantly alter convulsions. Thus presynaptic mechanisms such as synthesis and storage of both NE and DA appear to have little, if any, effect on pinealectomy-induced convulsions, whereas enhancing synaptic levels of NE by blocking its reuptake into adrenergic axons had an anticonvulsant effect. Further evidence suggesting a role for NE in modulating these convulsions is provided by the proconvulsant effect of blocking central beta-adrenergic receptors.

Journal ArticleDOI
TL;DR: Burned male Syrian hamsters exhibited reduced total (T4) and free (FT4) serum concentrations, a defect in T4 binding to serum proteins manifested by the T4 dialyzable fraction but not the in vitro T3 charcoal uptake, and reduced serum testosterone concentration.
Abstract: Burned male Syrian hamsters (burn size 23% of body surface) exhibited reduced total (T4) and free (FT4) serum concentrations, a defect in T4 binding to serum proteins manifested by the T4 dialyzable fraction but not the in vitro T3 charcoal uptake, and reduced serum testosterone concentration. These changes are similar to those noted previously in burned humans. Unlike such patients, burned hamsters did not exhibit reduced serum T3 nor elevated rT3 concentrations in a reproducible manner. Pinealectomy performed before burning in hamsters did not prevent the burn-induced depression in serum T4 and testosterone. {Endocrinology 117: 1090–1095,1985)

Journal Article
TL;DR: Investigation of the effects of pinealectomy and melatonin on the rat thyroid gland suggested that exogenous melatonin partially prevented stimulatory action of testosterone on the gland while neither PX nor melatonin modified estradiol effect on the glands.
Abstract: The aim of the study was to investigate, by means of stereology, the effects of pinealectomy (PX) and melatonin on the rat thyroid gland and to explain whether sex hormone effects on the gland are related to the presence of pineal gland. Gonadectomized rats of both sexes were employed, some of them were PX and on remaining sham surgery was performed. In appropriate groups rats were treated with melatonin, testosterone and estradiol. The volume of thyroid colloid, epithelium and stroma and the epithelium/colloid ratios were estimated by stereologic methods. Neither PX nor melatonin had a significant effect on the volume of principal histologic components of the thyroid gland and did not change epithelium/colloid ratio. Obtained data suggest that exogenous melatonin partially prevented stimulatory action of testosterone on the gland while neither PX nor melatonin modified estradiol effect on the gland.

Journal ArticleDOI
TL;DR: It was shown previously, on a model of amphetamine stereotypy, that behavior of this kind is an unsteady oscillatory process and stereotypy was assessed every minute for !
Abstract: Experiments were carried out on 34 noninbred male albino rats. As a first step the time course of stereotyped behavior of all the animals was determined after intraperitoneal injection of a standard dose (i mg/kg) of apomorphine. Stereotypy was recorded visually every 5 min until its complete disappearance, and the number of monotonous head movements during I min was counted. It was shown previously, on a model of amphetamine stereotypy, that behavior of this kind is an unsteady oscillatory process [I]. Accordingly, at the height of action of apomorphine (from the 20th to the 35th minute) stereotypy was assessed every minute for !5min.