Nicotinamide prevents the effect of perinatal asphyxia on dopamine release evaluated with in vivo microdialysis 3 months after birth.
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 microM) 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.
Bustamante
Diego
D
Programme of Molecular and Clinical Pharmacology, ICBM, Medical Faculty, University of Chile, PO Box 70.000, Santiago 7, Chile. dbustama@med.uchile.cl
Morales
Paola
P
Pereyra
Jorge Torres
JT
Goiny
Michel
M
Herrera-Marschitz
Mario
M
D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry / Q000379:methods; D005260:Female; D008297:Male; D017551:Microdialysis / Q000379:methods; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009536:Niacinamide / Q000008:administration & dosage*; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014803:Vitamin B Complex / Q000008:administration & dosage*
D000697:Central Nervous System Stimulants; D014803:Vitamin B Complex; D009536:Niacinamide; D011189:Potassium Chloride; D000661:Amphetamine; D004298:Dopamine