Perinatal hypothyroidism in rats: Persistent motivational and metabolic effects

Abstract

Five groups of female rats which were exposed to thiouracil for varying periods around the time of birth were compared with a 6th group of untreated controls in motivational, metabolic, and hormonal test situations during adolescence and adulthood. The thiouracil-treated rats displayed reduced fearfulness in lever-touching and lever-pressing tasks in operant conditioning chambers and in their initial adaptation to activity-wheel and maze apparatuses. These rats also showed hyperactivity in asymptotic running-wheel performance, increased spontaneous recovery of extinguished lever-pressing, and elevated responding in lever-pressing for variable-interval food reinforcement. A supplemental study revealed significantly greater ad libitum food and water intake and oxygen consumption in male thiouracil-treated rats and elevated serum thyroxine levels in thiouracil-treated females. In general the results indicate that perinatal thyroid deficiency engenders a chronic hypermetabolic state in both sexes which may be associated with a persistent, mild hyperthyroid condition in the case of female rats.

Evaluation and Characterization of the Hypothyroid <i>hyt/hyt </i>Mouse I: Somatic and Behavioral Studies

“…A relationship has been ob served between an alteration in neurotransmitters and re duced locomotor activities in these rats [24]. However, simi lar to our results, the effects of hypothyroidism caused no effect on activity, hypoactivity or hyperactivity depending on the age of testing [9,10,24,27] and perhaps on the dura tion. timing and method of production of hypothyroidism [7,9,17], Swimming escape involved the development of a coordi nated swimming behavior which encompasses reflexive behavior [28] as well as a learned response of escape.…”

“…In the mouse and rat, autonomous fetal thyroid hormone secretion rises after 16-17 days postconception followed by early neonatal in creases in T4 and subsequently T3. These increases in T4 have been shown to be temporally correlated with somatic development, brain differentiation, and behavioral deve lopment in the rat [11].The hypothyroid neonatal rat demonstrated somatic [8,16,17,29], neuroanatomical [11,12], electrophysiological [11,14] and behavioral abnormalities [7,9,10,14,17,19,22,24,27] [7,10,14,24] and hyperactivity [7,9,27] have been observed. Abnormalities in adaptive learned behavior [7,10,14,17,27] have been seen in more mature rats following neonatal or fetal hypothyroidism.…”

“…Abnormalities in adaptive learned behavior [7,10,14,17,27] have been seen in more mature rats following neonatal or fetal hypothyroidism. The hypo thyroid rats have also shown delayed vestibular system de velopment [ 12] and delayed and abnormal cerebellar devel opment and delayed cerebral cortical myelination and diffe rentiation [11,23].However, most of the behavioral and anatomical data has come from postnatal rodent hypothyroidism, resulting from surgically produced [ 17] or pharmacologically induced [7,9,10,22,27] hypothyroidism. The pharmacological agents employed to produce both fetal and neonatal hypo thyroidism such as propylthiouracil (PTU) [9,10,22,27] and methimazole [7] may have independent effects as well as causing both maternal and fetal hypothyroidism when given in utero [II].…”

“…The pharmacological agents employed to produce both fetal and neonatal hypo thyroidism such as propylthiouracil (PTU) [9,10,22,27] and methimazole [7] may have independent effects as well as causing both maternal and fetal hypothyroidism when given in utero [II]. Further, because of the difficulty in con trolling the duration of the pharmacological effects and the half-life of the existing T4, much of the fetal data has not been generated for the period related to autonomous fetal thyroid hormone secretion or brain differentiation but ra ther for various overlapping periods during the pregnancy.…”

Effects of Neonatal and Adult Thyroid Dysfunction on Thymic Oxytocin

“…Unfortunately, the MMI treatment could not be combined with the administration ofT) orT?. Hor monal replacement in rats rendered hypothyroid with thionamide drugs or 1311, is known to promote only a limited improve ment in somatic, biochemical and behavioral parameters, even after suspension of PTU or MMI administration [9, 20, 22, 31]. A toxic effect of thyroid hormone which in the rat must be given in amounts by far exceeding the physiological requirements (10], as well as a toxic interaction between the goitrogen used and Ti or T?…”