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Neonatal desipramine or zimeldine treatment causes long-lasting changes in brain monoaminergic systems and alcohol related behavior in rats

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Abstract

To study the relationship between neonatal antidepressant administration, active (REM) sleep and adult alcohol-related behavior, rat pups were treated daily with 5 mg/kg despramine (DMI) or 25 mg/kg zimeldine SC from the 6th to the 19th postnatal days. Movement sensitive mattress (“SCSB”) measurements showed that zimeldine treatment suppressed active sleep throughout the whole treatment period, but DMI was more effective during the first 8 days than during the last treatment days. At the age of 70 days, the zimeldine-treated rats expressed a selective increase of some components of activity in the open field test, and the DMI rats had a higher defecation score compared to the controls. Furthermore, the zimeldine-rats responded with a decrease in ambulation in the open field to an alcohol dose which generally stimulates locomotion in rats. At the age of 3 months the DMI and zimeldine rats showed increased voluntary intake of 10% (v/v) alcohol. Measurement of brain monoamines revealed that the neonatal treatment with DMI or zimeldine interfered with the normal development and function of the monoamine neuronal systems: the concentrations of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), and their metabolites were altered in several brain regions. The results thus suggest that neonatal treatment with DMI or zimeldine suppresses active sleep and has an influence on later alcohol-related behavior, possibly due to a long-lasting defect in brain monoaminergic transmission.

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Authors and Affiliations

  1. Department of Physiology, University of Helsinki, Siltavuorenpenger 20 J, SF-00170, Helsinki, Finland

    L. A. Hilakivi & D. Stenberg

  2. Research Laboratories of the Finnish State Alcohol Company (Alko Ltd), Box 350, SF-00101, Helsinki, Finland

    J. D. Sinclair & K. Kiianmaa

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  1. L. A. Hilakivi
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  2. D. Stenberg
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  3. J. D. Sinclair
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  4. K. Kiianmaa
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Hilakivi, L.A., Stenberg, D., Sinclair, J.D. et al. Neonatal desipramine or zimeldine treatment causes long-lasting changes in brain monoaminergic systems and alcohol related behavior in rats. Psychopharmacology 91, 403–409 (1987). https://doi.org/10.1007/BF00216004

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  • DOI: https://doi.org/10.1007/BF00216004

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