Nitric oxide and oxidative stress in the brain of rats exposed in utero to cocaine.
The role of nitric oxide (NO) and lipid peroxidation (LPO) processes in the physiological deficits induced by in utero cocaine exposure was examined in rats. NO generation in the hippocampus and cortex was detected using the electron paramagnetic resonance and LPO products were measured as thiobarbituric acid reactive species (TBARS). Pregnant Sprague-Dawley rats received a daily intraperitoneal injection of 20 mg/kg cocaine (IUC) or saline solution for control dams (IUV) between E17-E20. NO level was lower in the brain of IUC rats at postnatal day 1 and 2, but not 4, as compared with IUV rats. TBARS content was increased at day 1-4. Animals were used for behavioral testing at 25 days of age. Both NO and TBARS were elevated in the hippocampus of IUC rats as compared with IUV rats. Juvenile IUC rats developed significant learning impairments in the water-maze, as revealed by probe test retrieval deficits. Behavioral sessions resulted in a significant increase of TBARS levels only in IUV animals. Therefore, IUC rats showed a significant oxidative stress in basal conditions that may be related to their impaired learning ability. We did not find direct correlation between the changes in NO generation and intensity of LPO processes. It may probably mean that changes in intensity of LPO processes observed during prenatal cocaine exposure are not directly linked to NO pathway activation.
Bashkatova
Valentina
V
Institute of Pharmacology, Russian Academy of Medical Sciences, 8 Baltiyskaya Street, 125315, Moscow, Russia. bashkatovav@yahoo.com
Meunier
Johann
J
Vanin
Anatoly
A
Maurice
Tangui
T
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D007858:Learning / Q000187:drug effects; D008297:Male; D008431:Maternal-Fetal Exchange; D009569:Nitric Oxide / Q000502:physiology*; D018384:Oxidative Stress; D011247:Pregnancy; D011270:Pregnancy, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D003042:Cocaine