Prenatal hypoxia-ischemic affects neurons distribution in ventral tegmental area and nucleus accumbens, modifying memory in rats.

Prenatal hypoxia-ischemia (HI) is one of the major causes of mortality and chronic neurological diseases in newborns that can evoke permanent effects such as attention deficit hyperactivity disorder (ADHD), epilepsy and cerebral palsy. These damages are associated with a delay in neural development and death of neurons. Some of the cognitive deficits may be due to impairments in mesolimbic pathway. The ventral tegmental area (VTA) to the nucleus accumbens (NAc) pathway is involved in reward, attention, motivation and learning. Nitric oxide (NO) is a gas with many physiological functions, such as vasodilatation and neurotransmission, and it is produced by the oxidation of L-arginine through NOS, using NADPH-diaphorase (NADPH-d) as the electron donor. The aim of our study was to investigate the effects of prenatal HI on NO production in NAc and VTA by NADPH-d technique, a specific histochemical marker for NOS in the brain, and the effects on the motor and habituation by the open field test (OFT). HI was induced by clamping the uterine arteries of pregnant rats (Wistar) for 45 minutes, anesthetized intraperitoneally with Avertin® (2,2,2-Tribromoethanol, 250-500 mg/kg), on the 18th day of gestation (HI group). In the other group of females the surgery was the same, but without clamping the arteries (SHAM group - SH). Three groups were examined in behavior tests: HI, SHAM and CTRL (nom-manipulated group). The motricity and habituation of the pups in P90 were analyzed by OFT on 2 consecutive days. For NADPH-d histochemistry technique, rats from both groups (HI and SH) were intracardially perfused with saline and paraformaldehyde, and the brain was coronally sectioned. The experimental procedures were approved by the Institutional Animal Care and Use Committee (CEA/051/2009) and were conducted in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals. Data were compared with a one-way ANOVA, expressed by mean± SEM, and significance level was set at 5%. HI animals (n=16) did not show difference in motor behavior from first (37.1 ± 4.9) to second day of the test (37.8 ± 4.0), but a decreased activity was observed in SH (52.6 ± 6.0 on 1st day, 41.5 ± 6.8 on 2nd day, n=15) and CTRL (59.2 ± 5.8 on 1st day, 40.9 ± 5.4 on 2nd day, n=16) groups. There was no difference in motricity between groups. HI animals showed a decreased number of NADPH-d positive neurons (216±66.36 in NAc; 150±16.7 in VTA, n=3) compared to SHAM (358±119.9 in NAc; 274±48.42 in VTA, n=3) group (preliminary data). Our findings showed that HI impairs habituation but not the motor activity, and also affects NADPH-d-positive neurons distribution in NAc and VTA. [ABSTRACT FROM AUTHOR]