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Nicotinamide prevents the effect of perinatal asphyxia on dopamine release evaluated with in vivo microdialysis 3 months after birth

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Abstract

The present study shows that nicotinamide prevents the long-term effect of perinatal asphyxia on dopamine release monitored with in vivo microdialysis in the neostriatum of 3-month-old rats. Perinatal asphyxia was induced by immersing foetuses-containing uterine horns removed from ready-to-deliver rats into a water bath for 16 or 20 min. Sibling, spontaneous, and caesarean-delivered pups were used as controls. Saline or nicotinamide (0.8 mmol/kg, i.p.) was administered to control and asphyxia-exposed animals 24, 48, and 72 h after birth. After weaning, the rats were randomly distributed in laboratory cages for animal care under standard ad libitum laboratory conditions. Approximately 3 months after birth, control and asphyxia-exposed animals were implanted with microdialysis probes into the lateral neostriatum for measuring extracellular monoamine and metabolite levels with HPLC-coupled to an electrochemical detection system under basal, D-amphetamine, and K+-depolarising conditions. There was an asphyxia-dependent decrease of extracellular dopamine levels, mainly observed during the periods when D-amphetamine (100 μM) or KCl (100 mM) was added into the perfusion medium. Compared to that observed in caesarean-delivered controls, the effect of D-amphetamine on dopamine levels was decreased by approximately 30 and 70% in animals exposed to 16 and 20 min of perinatal asphyxia, respectively. The effect of K+-depolarisation was decreased by 45 and 83% in animals exposed to the same periods of asphyxia, respectively. Both effects were prevented by nicotinamide, even if the treatment started 24 h after the insult. The present results support the idea of nicotinamide as an interesting molecule, useful for protecting against anoxia/ischemia occurring at neonatal stages. Nicotinamide can help to restore NADH/NAD+ depletion, but also to inhibit PARP-1 overactivation, a mechanism of action that has attracted attention, representing a novel target for neuroprotection following insults involving energy failure.

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Acknowledgments

This study was supported by grant no.103-0521 from FONDECYT-Chile. We would like to acknowledge the excellent technical assistance of Mr. Juan Santibañez and Ms. Carmen Almeyda, Medical Faculty, University of Chile.

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Authors and Affiliations

  1. Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, PO Box 70.000, Santiago, 7, Chile

    Diego Bustamante, Paola Morales & Mario Herrera-Marschitz

  2. Department of Paediatrics, Medical Faculty, University of Chile, PO Box 70.000, Santiago, 7, Chile

    Jorge Torres Pereyra

  3. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

    Michel Goiny

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  1. Diego Bustamante
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  2. Paola Morales
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Correspondence to Mario Herrera-Marschitz.

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Bustamante, D., Morales, P., Pereyra, J.T. et al. Nicotinamide prevents the effect of perinatal asphyxia on dopamine release evaluated with in vivo microdialysis 3 months after birth. Exp Brain Res 177, 358–369 (2007). https://doi.org/10.1007/s00221-006-0679-0

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