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Altered exploratory behavior and brainstem catecholamine concentrations in rats neonatally exposed to mild normobaric hypoxia

Perinatal hypoxic-ischemic brain injury often leads to serious neurological and/or cognitive impairments. However, mild hypoxic events during an early mid-gestation may cause subtle motor, sensory and behavioral deficits that become detectable only later in life, unabling so an early intervention. In order to search for early behavioral, neurochemical, structural and molecular markers of mild hypoxia, we have developed a corresponding rat model by exposure of 1-day-old pups (PND1) to hypoxic conditions (8% O2, 92% N2) in a normobaric chamber for 2 hours. This study was aimed at detection of possible changes in exploratory and anxiety-like behavior, as well as in concentrations of brainstem catecholamines known to have significant impact on these well-conserved adaptive behaviors, in the mentioned rat model. On PNDs 33-36, 29 hypoxic and 27 control rats were tested in an open field (OF) and on a hole board (HB). On PND50, brainstem samples of 16 hypoxic and 15 control rats were collected for dopamine (DA) and noradrenaline (NA) determination by 2-CAT ELISA. Compared to control rats, hypoxic rats did not differ in the level of locomotion (total distance travelled in OF) and anxiety-like behavior (% of visited inner holes in HB). On the other hand, they displayed significant alterations in exploratory behavior – increased rearing and decreased total number of visited holes, which may be interpreted as increased vigilance, difficulties in spatial mapping, or impaired sensory processing. Neurochemical measurements, showing unchanged NA levels and a three-fold increase in DA levels in midbrains of hypoxic group, point to the two latter possibilities. In conclusion, we have demonstrated that neonatal exposure of rat pups to mild acute hypoxia can induce subtle behavioral changes paralleled by midbrain dopamine imbalance. Future structural and gene expression studies in the specific brain regions (e.g. thalamo-cortical communication, hippocampus) should reveal possible mechanism of the observed alterations.

non-invasive model ; perinatal brain injury ; rearing ; dopamine ; noradrenaline

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