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Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors in the caudate/putamen

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Summary

Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D1 (3[H]SCH 23390) and D2 (3[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither3[H]SCH 23390 nor3[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.

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Author notes

  1. I. Hilakivi

    Present address: Department of Physiology, Institute of Biomedicine, University of Helsinki, Helsinki

Authors and Affiliations

  1. Department of Physiology, Institute of Biomedicine, University of Helsinki, Helsinki

    T. Taira

  2. Department of Pharmacy, Division of Pharmacology and Toxicology, University of Helsinki, Helsinki

    L. Ahtee & L. M. J. Attila

  3. Department of Neurology, University of Turku, Turku, Finland

    J. O. Rinne & P. Marjamäki

Authors
  1. I. Hilakivi
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  2. L. Ahtee
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  3. J. O. Rinne
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  4. T. Taira
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  5. L. M. J. Attila
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  6. P. Marjamäki
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Hilakivi, I., Ahtee, L., Rinne, J.O. et al. Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem, caudate/putamen and cortex, and on dopamine D1 and D2 receptors in the caudate/putamen. J. Neural Transmission 102, 139–148 (1995). https://doi.org/10.1007/BF01276509

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  • DOI: https://doi.org/10.1007/BF01276509

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