Nonresponsiveness of the thyroid gland to goitrogen in the early neonatal period in the rat: light- and electron-microscopic observations.

The thyroid response of fetal and neonatal rats to propylthiouracil (PTU) as a goitrogen was studied with observation of the thyroid glands by light and electron microscopy. On day 19 of gestation and on days 1, 3, 5 and 8 after birth, fetal and neonatal rats were given a subcutaneous injection of PTU and were autopsied 2 days later. PTU induced conspicuous goiters in fetal rats but did not in neonatal rats aged up to day 5 after birth. Beyond that age, PTU again induced goiters. Histologically, the follicular cell height in goitrous thyroid glands was significantly increased. Ultrastructurally, follicular cells in goitrous thyroid glands often had colloid droplets and lysosomes. It seems that nonresponsiveness of the thyroid glands in early neonatal rats to goitrogen is due to a temporary decline of the pituitary activity of thyrotropin secretion. About 5 days or more after birth, the pituitary-thyroid system begins to operate again in response to goitrogen.     

Thyroid hypoplasia as a cause of congenital hypothyroidism in Williams syndrome

In the Williams-Beuren syndrome (WBS), disorders of the thyroid function and morphology have been reported and programs of thyroid screening and surveillance are recommended. However, the frequency of biochemical thyroid assessment, particularly in the first year of life, is being debated. In this report we describe an infant with WBS and congenital hypothyroidism, due to an important thyroid hypoplasia. The patient, a 1-month-old female, negative at primary neonatal thyroid screening, was referred to our hospital for dyspnea. Thyroid function tests showed a raised TSH (42 mIU/l; normal range 0.5-4 mIU/l) with a low FT(4) concentration (10.21 pmol/l; normal range: 10.29-24.45 pmol/l). Ultrasound examination of the neck showed a significant thyroid hypoplasia, whereas (99m)Tc-pertechnetate thyroid scintigraphy evidenced a thyroid gland in normal position, with reduced shape and overall weak fixation. Therefore, treatment with L-thyroxinewas started. Thyroid hypoplasia is a frequent characteristic of WBS and abnormalities of thyroid function are common in patients with this feature. Therefore, the possibility of congenital hypothyroidism should always be taken into consideration too and, even if congenital hypothyroidism neonatal screening is negative, thyroid (morphology and function) evaluation should be regularly assessed when the diagnosis is made and, thereafter, every year in the first years of life.     

Ontogeny of renal renin in congenital hypothyroid rats.

In the present study we have found age-related differences between the renal renin activity (RRA) and the immunoreactive renal renin (IRR) profiles during the neonatal development of the rat. RRA was markedly greater in newborn rats than in adult ones, while IRR was low at birth and progressively increased until adulthood. These observations suggest the existence of a control mechanism operating either at the level of the translation of the template or at a post-translational level which varies throughout the development. Since thyroid hormones have been demonstrated to affect several renin-angiotensin components, the neonatal RRA and IRR profiles in congenital hypothyroid rats were evaluated to determine whether renal renin activity or its synthesis could be endogenously regulated by thyroid hormones in the early stages of life. Although significant differences were observed in the RRA profiles of congenital hypothyroid and control rats, no changes were found in the relative amount of immunoreactive protein. These findings indicate that thyroid hormone deficiency does not directly affect renal renin expression during the critical period of the normal morpho-functional development of the newborn.     

Hormone synthesis and storage in the thyroid of human preterm and term newborns: effect of thyroxine treatment.

Iodine and thyroglobulin concentrations, as well as iodine, T3, T4 and sialic acid contents of thyroglobulin, were measured in thyroid glands collected postmortem from 42 human premature or term newborns and infants. Three groups were considered: very preterm newborns (24-32 postmenstrual weeks, < 5 days postnatal life), preterm and term newborns (34-41 postmenstrual weeks, < 5 days postnatal life) and infants (born at term, postnatal age 1-8 months). Five very preterm and seven preterm newborns received a daily dose of 10 microg/kg L-T4 for at least 3 days. Thyroid weight and sialic acid content of thyroglobulin progressed with maturation. Intrathyroidal concentrations of iodine and thyroglobulin did not increase significantly before the 42nd week of postmenstrual age. The level of thyroglobulin iodination increased during the postnatal life, except in the very preterm neonates. T4 and T3 content of thyroglobulin was directly proportional to its degree of iodination and positively related to its sialic acid content. L-T4 treatment of preterm newborns increased thyroglobulin iodination and T4-T3 content, without increasing thyroglobulin concentration in the thyroid. It was concluded that the storage of thyroglobulin and iodine in the thyroid develops around term birth. This, associated with the resulting rapid theoretical turnover of the intrathyroidal pool of T4 in Tg, could be an important factor of increased risk of neonatal hypothyroxinemia in the premature infants. The L-T4 treatment of preterm newborns does not accelerate the maturational process of the thyroid gland.     

Prenatal exposure of the fetal rat to excessive L-thyroxine or 3,5-dimethyl-3'-isopropyl-thyronine produces persistent changes in the thyroid control system

Studies were conducted to determine if brief exposure, in utero, to high levels of T4 or to the synthetic thyromimetic agent 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) can produce permanent disruption of the thyroid control system in a manner analogous to the changes in the "set point" reported to occur due to neonatal T4 exposure in the "neo-T4 syndrome". If such a change were to occur, it could explain the persistent thyroid disturbances seen in the progeny of hypothyroid mother rats. These latter progeny are exposed in utero to both low and high serum T4 levels. Maternal T4 treatment produced a 4-fold elevation in fetal serum T4 accompanied by a large decrease in serum TSH levels. The brief treatment in utero with high doses of T4 or of DIMIT resulted in higher neonatal mortality and the T4-treatment produce subsequent growth stunting. These treatments resulted in suppression of the fetal/neonatal thyroid which was very apparent at 5 days of age. At 30 days post-partum, the thyroid control system of the progeny of the T4 and DIMIT-treated animals was still abnormal with low serum T4 levels accompanied with normal serum TSH and T3 levels. At 60 days of age, serum T4 levels remained low in the progeny of the T4-treated animals and the TSH response to TRH was subnormal in both the progeny of the T4-treated and the DIMIT-treated animals. However, serum and pituitary TSH and serum T3 were normal. The thyroid control system of the rat is sensitive to prenatal exposure to hyperthyroxinemia as it is to postnatal exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hypergravity exposure on the developing central nervous system: possible involvement of thyroid hormone

The present study examined the effects of hypergravity exposure on the developing brain and specifically explored the possibility that these effects are mediated by altered thyroid status. Thirty-four timed-pregnant Sprague-Dawley rats were exposed to continuous centrifugation at 1.5 G (HG) from gestational Day 11 until one of three key developmental points: postnatal Day (P) 6, P15, or P21 (10 pups/dam: 5 males/5 females). During the 32-day centrifugation, stationary controls (SC, n = 25 dams) were housed in the same room as HG animals. Neonatal body, forebrain, and cerebellum mass and neonatal and maternal thyroid status were assessed at each time point. The body mass of centrifuged neonates was comparatively lower at each time point. The mass of the forebrain and the mass of the cerebellum were maximally reduced in hypergravity-exposed neonates at P6 by 15.9% and 25.6%, respectively. Analysis of neonatal plasma suggested a transient hypothyroid status, as indicated by increased thyroid stimulating hormone (TSH) level (38.6%) at P6, while maternal plasma TSH levels were maximally elevated at P15 (38.9%). Neither neonatal nor maternal plasma TH levels were altered, suggesting a moderate hypothyroid condition. Thus, continuous exposure of the developing rats to hypergravity during the embryonic and neonatal periods has a highly significant effect on the developing forebrain and cerebellum and neonatal thyroid status (P < 0.05, Bonferroni corrected). These data are consistent with the hypothesized role of the thyroid hormone in mediating the effect of hypergravity in the developing central nervous system and begin to define the role of TH in the overall response of the developing organism to altered gravity.     

Developmental delay and unstable state of the testes in the rdw rat with congenital hypothyroidism

From the present study of the rdw rat, it is clear that the thyroid hormone is essential for the development and maintenance of the testes. In previous studies, the thyroid hormone has few serious effects on the testes except during the neonatal stage when the thyroid hormone receptor is mainly present. However, there is little knowledge concerning the prolonged effect of thyroid hormone deficiency throughout the rat's life span. In the present study, a morphological analysis was performed on the testes of rdw rats with congenital hypothyroidism. The rdw testes required a longer time to develop into the normal adult structure. Moreover, the developed, normal structure began to degenerate after full maturation. Specific characteristics of the rdw testes include: (i) a prolonged proliferation of Sertoli cells during postnatal development; (ii) a developmental delay in the appearance of spermatocytes and spermatid; (iii) direct contact with each other for both spermatocytes and spermatids, without Sertoli cell cytoplasm completely intervening between adjacent germ cells; (iv) subsequent apoptosis of germ cells after maturation; (v) reduction in the height of the seminiferous epithelium; and (vi) lower testosterone levels in the rdw rats, especially during old age. Thus, we conclude that the thyroid hormone plays an important role in developing and maintaining normal function of testes.     

Thyroid function in the newborn lamb. Physiological approach of the mechanisms inducing the changes in plasma thyroxine, free thyroxine and triiodothyronine concentrations

Several experiments were performed to study the mechanisms inducing the neonatal rises in plasma iodothyronine concentrations in lambs. TSH levels rose during the first 4 to 8h of life, whereas plasma T4 an T3 concentrations increased only from birth to respectively 2 and 1h; the rise in free T4 levels was longer and more important than the rise in total T4. Only T4 changes were strongly related to the extent of TSH increase. The neonatal TSH surge was inhibited by delaying the first milk intake, indicating a great importance of the early nutritional status; in these conditions, the neonatal T4 rise did not occur, whereas the T3 increase was not affected; therefore, in contrast to T4, the T3 increase occurring at birth is not TSH-dependent. As in thyroidectomized lambs continuously infused with T4, plasma T3 concentrations did not increase at birth, it appears that the neonatal T3 surge probably has a thyroidal origin. These results raise the possibility of the existence of a specific stimulator of thyroidal T3 secretion, at least in the newborn lamb. In addition, comparison of the respective T4 increases, at birth or after TSH stimulation in 24 h-old animals, suggests that the ability of the thyroid to respond to a sustained stimulation is strongly reduced at birth. Lastly, neonatal changes in the affinity and/or capacity of carrier proteins for T4, perhaps partly induced by the observed simultaneous rise in free fatty acid levels, could explain that plasma T3 concentrations remained elevated despite a decrease in total T4 levels from 2 h after birth.     

Thyroid function and body weight programming by neonatal hyperthyroidism in rats - the role of leptin and deiodinase activities.

Several authors have shown that secondary hypothyroidism was programed by neonatal thyroxine (T4) treatment. However, the associated changes of body weight (BW) were less studied, especially those related to the body fat proportion. Here, we have evaluated the effect of neonatal thyroxine treatment on BW, fat proportion, serum leptin, and thyroid function of 60-day-old rats. Wistar rats were treated with thyroxine (50 microg/100 g BW, ip) (T) or saline (S), during the first 10 days of life. BW, nose-rump length (NRL), and food consumption were monitored for 60 days, when the animals were sacrificed. Thyroid function was evaluated by thyroid radioiodine uptake (RAIU), serum T3, T4, TSH, and liver mitochondrial alpha-glycerophosphate dehydrogenase (mGPD) and type 1 and 2 deiodinases (D1 and D2) activities, which are thyroid hormone-dependent enzymes. T animals showed lower food intake, BW and NRL, but higher total fat mass (+33%) and serum leptin (+46%). They also showed lower serum T3 (-23%), T4 (-32%), TSH (-36%), RAIU (-29%) and mGPD activity (-22%). Hypothalamic and pituitary D2 activities were higher (+24% and 1.4 fold, respectively), while brown adipose tissue (BAT) D2 and skeletal muscle D1 activities were lower (-30% and -62%, respectively). Thus, neonatal hyperthyroidism programs for a higher fat proportion and hyperleptinemia, which can explain the lower food intake. The TH-dependent enzymes activities changed accordingly, except for the decrease in BAT D2, which may be due the role played by the hyperleptinemia. Finally, the decrease in peripheral deiodination may contribute to a lower me-tabolic rate that may increase the adiposity.     

Influence of experimental acidosis on the concentrations of thyreostimulin (TSH) and iodothyronines (total T4, free T4, T3) in the plasma of the newborn lamb

The effects of acute acidosis on neonatal thyroid function were studied by infusing HCl for 4 h in 42 to 54-h-old lambs. Animals of the same age, used as controls, were simultaneously infused with physiological saline. HCl infusion induced a sharp decrease in blood pH and total restoration did not occur before 48 h. When compared to control lambs, this experimental acidosis was associated with slight, but significant, decreases in plasma TSH, total T4, free T4 and total T3 levels, and in values of the free T4/total T4 ratio; the T3/FT4 ratio was not affected. The values of RT3/FT4 ratio were significantly increased in acidotic lambs. It is concluded that acidosis induced only modest secretory changes in neonatal thyroid function and slightly reduced the proportion and the amount of free T4.     

Effects of neonatal hypothyroidism on rat brain gene expression.

To define at the molecular biological level the effects of thyroid hormone on brain development we have examined cDNA clones of brain mRNAs and identified several whose expression is altered in hypothyroid animals during the neonatal period. Clones were identified with probes prepared by subtractive or differential hybridization, and those corresponding to mRNAs altered in hypothyroidism were further studied by Northern blot analysis. Using RNA prepared from whole brains, no effect of hypothyroidism was found on the expression of the astroglial gene coding for glial fibrillary acidic protein. Among genes of neuronal expression, no significant alterations were found in the steady state levels of mRNAs coding for neuron-specific enolase, microtubule-associated protein-2, Tau, or nerve growth factor. N-CAM mRNA increased slightly in hypothyroid brains. In contrast a 2- to 3-fold decrease was found in the mRNA coding for a novel neuronal gene, RC3. This is the first neuronal gene known to be significantly altered at the mRNA level by thyroid hormone deprivation. The abundance of the mRNAs for the major myelin proteins proteolipid protein, myelin basic protein, and myelin-associated glycoprotein, expressed by oligodendrocytes, were also decreased in hypothyroid brains. Developmental studies on RC3 and myelin-associated glycoprotein expression indicated that the corresponding mRNAs accumulate in the brain of normal rats during the first 15-20 days of neonatal life. A similar accumulation occurred in hypothyroid brains, but at much reduced levels. The results demonstrate that thyroid hormone controls the steady state levels of particular mRNAs during brain development.     

Hypothyroidism in the fetal and neonatal rat does not impair the insulin secretory response to glucose

Fetal and neonatal hypothyroidism was induced by treating pregnant rats with propylthiouracil (PTU) in the drinking water from day 12 of gestation to day 7 postnatally. The serum levels of thyroxine and triiodothyronine were lowered in both mother and offspring and the neonates showed a 20% reduction in weight gain. An i.p. glucose tolerance test on the 7-day old neonates revealed no major disturbances in glucose tolerance or insulin response. The data suggest that thyroid hormones are not essential for the neonatal development of the B-cell secretory response to glucose.     

丙基硫氧嘧啶影响妊娠合并甲状腺功能亢进孕妇甲状腺功能及妊娠结局的研究

目的:探讨丙基硫氧嘧啶(PTU)影响妊娠合并甲状腺功能亢进(甲亢)孕妇甲状腺功能及妊娠结局的影响。方法:选择我院妇产科2010年3月至2013年1月收治的110例妊娠合并甲亢的患者作为观察对象,随机分为观察组58例,对照组52例。观察组予PTU每天300 mg口服,对照组确诊后未能定期检测甲状腺功能而自行停药,或拒绝PTU药物治疗。结果:观察组TT3、TT4、FT3、FT4、TSH水平均显著低于对照组,差异均具有统计学意义(均P0.05);观察组早产或流产、剖宫产、妊娠高血压、心力衰竭、重度子痫明显低于对照组,而足月产明显高于对照组,差异均具有统计学意义(均P0.05);观察组的围生儿发生胎儿窘迫、低体重儿、新生儿甲亢、转入NICU发生率均显著低于对照组,两组比较差异均具有统计学意义(均P0.05)。结论:规范的PTU治疗能很好地改善妊娠合并甲亢患者的孕期甲状腺功能,减低甲亢对孕妇及新生儿的危害,改善妊娠结局,且对新生儿畸形率无显著的影响,是一种相对安全和有效的治疗方法。     

Evidence for the role of brain biogenic amines in depressed motor activity seen in chemically thyroidectomized rats.

Abstract— The effects of exposure to an antithyroid drug, methimazole, on brain tyrosine hydroxylase and tryptophan hydroxylase activity, as well as the levels of norepinephrine, dopamine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid have been investigated in maturing brain. Daily treatment of neonatal rats with methimazole for 30 days induced chemical thyroidectomy as evidenced by significant impairment of body and brain growth. The activities or brain tyrosine hydroxylase and tryptophan hydroxylase and the levels of norepinephrine, dopamine and 5-hydroxytryptamine were markedly altered in a dose- and time-dependent manner in methimazole-treated rats. Conversely, the concentration of brain 5-hydroxyindoleacetic acid was elevated (46%) by methimazole administration. Treatment with the antithyroid drug failed to exert any significant effect on the endogenous levels of brain tryptophan, as well as on the activity of the deaminating enzyme, monoamine oxidase. Administration of triiodothyronine (25 or 100 μg/100 g) to hypothyroid rats for 30 days did not produce any appreciable effect upon the neurochemical parameters related to either norepinephrine or 5-hydroxytryptamine mctabolism. However, increasing the dose of triiodothyronine to 250 μg/100 g significantly elevated the levels of norepinephrine and 5-hydroxytryplamine as well as the activities of the two synthesizing enzymes, tyrosine hydroxylase and tryptophan hydroxylase. Brain 5-hydroxyindoleacetic acid levels were restored to normal values in thyroid hormone-deficient rats treated with this higher dose of triiodothyronine. Evidencc also was obtained to show that chemical thyroidectomy suppressed the spontancous locomotor activity in neonatal rats; the changes being apparent at 15 days of age. Our data support the view that thyroid hormone in neonatal life displays an important regulatory effect on the metabolism of norepinephrine, dopamine and 5-hydroxytryptamine. Since certain amines have been known to be implicated as the neurochemical substrates for behavioural arousal, it is conceivable that the observed hypoactivity in methimazolc-treated rats may, at least in part, be related to impaired maturation of norepinephrine and dopamine-synthesizing systems in brains of cretinous rats.     

Sequential analysis of experimental autoimmune thyroiditis induced by neonatal thymectomy in the Buffalo strain rat

We have studied the evolution of thyroiditis induced by neonatal thymectomy in Buffalo strain rats, with particular emphasis on the thyroid lymphocytic infiltrate. The earliest change was increased endothelial Ia expression, and infiltration of the thyroid at 5 weeks by ED1- and ED2-positive macrophages and B and T cells. The T cells comprised equal numbers of Ox 8 (T cytotoxic/suppressor)- and W3/25 (T helper)-positive cells. Ia-positive thyroid follicular cells were seen only in the presence of a T-cell infiltrate. Thyroglobulin antibody levels, thyroid weight, thyroid follicular cell Ia expression, and lymphocytic infiltration of the thyroid were maximal between Weeks 12 and 24, and impairment of macrophage function by injection of silica at this time produced amelioration of disease. The thyroid weight returned to control levels by Week 34 and Ia expression by thyroid cells disappeared. Circulating Ox 8-positive T cells were reduced between Weeks 12 and 24 and by Week 34 had returned to control levels. Our results indicate that the mononuclear infiltrate precedes thyroid follicular cell Ia expression and macrophages play an important role in perpetuating thyroiditis. Recovery from disease is accompanied by a return to normal in circulating suppressor/cytotoxic T cells.     

Long-lasting ill-effects of neonatal qualitative and/or quantitative dysnutrition in the human

Qualitative dysnutrition (pure bottle-feeding) as well as quantitative dysnutrition (overnutrition as well as undernutrition) during the first trimenon of postnatal life was found to lead to long-lasting mental, psychic and/or physical ill-effects in the human. Females who were completely bottlefed during neonatal life showed significantly decreased school achievements as well as significantly decreased learning capacity and social adaptability at 16 years of age as compared to females who were purely breastfed or breast- plus bottlefed in neonatal life. Males who were artificially overfed during neonatal life also showed significantly decreased school achievements and significantly decreased learning capacity in adolescence as compared to males with normal weight development in neonatal life.     

Hereditary pituitary dwarfism in mice affects skeletal and cardiac myosin isozyme transitions differently

The dwarf mutation in mice interferes with the development of those anterior pituitary cells responsible for production of thyroid stimulating hormone, growth hormone, and prolactin. Myosin isozyme transitions in both cardiac and skeletal muscle were also found to be affected in this mutant. Electrophoresis of native myosins demonstrated that the fetal (V3) to adult (V1) ventricular cardiac isozyme transition was completely blocked in dwarf mice; in contrast, the neonatal to adult fast myosin transition in hind limb skeletal muscle was slowed but not totally inhibited. The persistence of neonatal myosin heavy chain for up to 55-75 d after birth in dwarf mice, as compared with 16 d in normal mice, was directly demonstrated by polypeptide and immunopolypeptide mapping. Morphological examination of 18-36-d-old dwarf skeletal muscles by optical and electron microscopy revealed a relative immaturity, but no signs of gross pathology were evident. Immunocytochemical analysis showed that the abnormal persistence of neonatal myosin occurs in most of the fibers. Multiple injections of thyroxine restored a normal isozyme complement to both cardiac and skeletal muscles within 11-15 d. Therefore, the effects of the dwarf mutation on myosin isozymes can be explained by the lack of thyroid hormone in these animals. Because the synthesis of growth hormone is not stimulated by thyroid hormone in dwarf mice as it would be in normal animals, these results demonstrate that thyroid hormone promotes myosin isozyme transitions independent of growth hormone production.     

Effects of anti-thyrotropin-releasing hormone anti-serum treatment during the neonatal period on the development of rat thyroid function

Effects of anti-thyrotropin-releasing hormone (TRH) anti-serum treatment during the neonatal period on the development of rat thyroid function were studied. On postnatal days 2 and 4, rats were administered anti-TRH anti-serum ip, and they were serially decapitated at the 4th, 8th and 12th week after birth. TRH, thyrotropin (TSH), thyroxine (T4) and 3,3',5-triiodothyronine (T3) were measured by radioimmunoassay. Immunoreactive TRH (ir-TRH) in the hypothalamus did not change significantly after anti-TRH anti-serum treatment, and plasma ir-TRH tended to decrease. The plasma ir-TRH and TSH responses to cold were significantly inhibited. The plasma TSH response to TRH was also significantly inhibited. The plasma basal TSH levels were significantly lower than in controls. The plasma T4 and T3 levels were found to be lower than those in the controls. Findings suggested that treatment with anti-TRH anti-serum during the neonatal period disturbed the development of rat thyroid function, inhibiting TRH release and altering thyrotroph sensitivity to TRH.     

Brain biogenic amines and altered thyroid function.

Evidence has been presented that alterations in thyroidal status produce marked changes in the metabolism of several biogenic amines in developing brain. Neonatal hypothyroidism induced either by ¹³¹I or by an anti-thyroid agent, methimazole, markedly decreased the concentrations of norepinephrine, dopamine and 5-hydroxytryptamine and the activity of their rate-limiting enzymes, tyrosine hydroxylase and tryptophan hydroxylase. However, the levels of 5-hydroxyindoleacetic acid, the chief metabolite of 5-hydroxytryptamine were elevated in several regions of the brain. Whereas thyroid deficiency in early life produced no appreciable change in whole brain monoamine oxidase activity, it was increased in mid brain and decreased in the hypothalamus. Brain acetylcholine levels were significantly elevated and the activity of acetylcholinesterase remained unchanged in rats made hypothyroid at 1 day of age. Delaying thyroidectomy for 20 days after birth produced less appreciable changes in norepinephrine and 5-hydroxytryptamine metabolism. Thyroid deficiency suppressed the ontogenesis of behavioural arousal and spontaneous locomotor activity. The administration of L-triiodothyronine to hypothyroid animals in early life restored the metabolism of various neurohumors virtually to the normal limits. However, when the replacement therapy was postponed until adulthood, L-triiodothyronine failed to produce any restorative effects, suggesting that a critical period exists in early life during which thyroid hormone must be present to permit normal developmental pattern of central amines. Data also have been obtained demonstrating that neonatal hyperthyroidism induced by daily administration of L-triiodothyronine results in an increased turnover of norepinephrine and 5-hydroxytryptamine. These amine changes were accompanied by a marked rise in the spontaneous locomotor activity in hyperthyroid rats. Finally, chronic treatment with lithium, an antimanic drug, also known to suppress thyroid hormone production, significantly decreased not only the spontaneous locomotor activity, but also changes in the turnover of 5-hydroxytryptamine and norepinephrine in neonatally hyperthyroid rats.