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  • 1975-1979  (2)
  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1463
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Administration of a single dose (10 mg/kg) of a relatively new benzodiazepine, bromazepam to rats markedly suppressed their spontaneous locomotor activity. Hypomobility became apparent 15 min after the injection and remained significantly lower during the period of observation for 6 hours when locomotor activity was 27% of controls. Following 2 hours after bromazepam treatment, no change was noted in tyrosine levels and tyrosine hydroxylase activity in striatum or rate of catecholamine synthesis in synaptosomal preparation (P2 pellet). However, the endogenous levels of norepinephrine, dopamine and 5-hydroxytryptamine were significantly increased not only in several brain areas examined, but also in p2 pellet. Bromazepam failed to change3H-norepinephrine and3H-5-hydroxy-tryptamine uptake in synaptosomes suggesting that the increased levels of monoamines are not related to alterations in uptake mechanisms, but probably to a diminished release. This is supported by the data on striatal homovanillic acid and whole brain 4-hydroxy-3-methoxyphenyl glycol whose concentrations were significantly lowered following a single injection of this benzodiazepine. However, bromazepam increased 5-hydroxyindoleacetic acid levels in hypothalamus, mid-brain and pons-medulla. The present study demonstrates that bromazepam elicits its tranquilizing action by lowering the release of catecholamines in brain; however, its anti-anxiety action might be associated with a reduction in 5-hydroxytryptamine turnover. Our data also suggest that bromazepam is almost as potent as diazepam in altering the metabolism of certain putative neurotransmitters in brain.
    Type of Medium: Electronic Resource
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