Abstract
The influence of neonatal hypothyroidism on norepinephrine and dopamine metabolism in certain discrete regions of rat brain was studied. Intraperitoneal administration of 131I in a dose of 200 μCi to 1-day-old rats significantly impaired the ontogenesis of spontaneous locomotor activity and reduced tyrosine hydroxylase activity (by 35%) in the striatal region. A parallel decrease in norepinephrine levels was observed in hypothalamus, pons-medulla and striatum. Thyroid deficiency in neonatal life also decreased dopamine levels as well as its metabolite, 3,4-dihydroxyphenylacetic acid, in striatal region. A comparable, but statistically non-significant, change was observed in homovanillic acid as well. Whereas neonatal hypothyroidism decreased monoamine oxidase activity (by 14%) in the hypothalamus, a rise was noted in the mid-brain region. Hypothyroidism in young rats significantly increased catechol-O-methyl transferase activity in brain stem, striatum and mid-brain; however, a 40% decline in O-methylating enzyme was observed in hypothalamus. Data suggest that low levels of norepinephrine, dopamine and their metabolites can be attributed to the decreased synthesis and utilization of these catecholamines in brain. Replacement therapy with L-triiodothyronine (10 μg/100 g, s.c.) for 25 days, beginning 5 days after radiothyroidectomy, enhanced tyrosine hydroxylase activity and raised norepinephrine, dopamine and 3,4-dihydroxyphenylacetic acid levels to virtually normal values. Furthermore, the locomotor activity was significantly increased in hypothyroid rats given L-triiodothyronine treatment in infancy. However, when the initiation of L-triiodothyronine treatment was postponed until adulthood, no significant changes was observed in tyrosine hydroxylase or in norepinephrine and dopamine levels of rat brain. These findings are discussed in relation to the role of catecholamines in depressed behaviour seen during ‘cretinoid’ syndrome and the importance of thyroid hormone during the critical period of maturation of brain monoaminergic neurons.
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Rastogi, R.B., Singhal, R.L. Effect of neonatal hypothyroidism and delayed L-triiodothyronine treatment on behavioural activity and norepinephrine and dopamine biosynthetic systems in discrete regions of rat brain. Psychopharmacology 62, 287–293 (1979). https://doi.org/10.1007/BF00431960
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DOI: https://doi.org/10.1007/BF00431960