Maternal para-chlorophenylalanine exposure modifies central monoamines and behaviors in the adult offspring.

We reported a perspective animal model of neurodevelopmental disorders using rats prenatally exposed to an inhibitor of serotonin (5HT) synthesis, para-chlorophenylalanine (PCPA). Earlier, we demonstrated that prenatal exposure to PCPA caused fetal 5HT depletion and changes both in open field activity and in depression-related behavior, as well as impairments in spatial learning in the adult offspring (Vataeva et al., 2007). The present study revealed that prenatal PCPA treatment resulted in the offspring's significantly reduced anxiety-related behavior in the elevated plus-maze and reduced neophobia to intake fluids in a novel environment. These effects are accompanied by hedonic changes in the form of an appropriate increase in saccharin preference. We confirmed our earlier finding that prenatal PCPA exposure affected the open field locomotor activity. In the present study we have shown that the selective 5HT reuptake inhibitor (SSRI) paroxetine decreases locomotor activity in the prenatally PCPA-treated offspring. It was also found that in the PCPA-treated fetal brain, 5HT depletion was associated with a significant decrease in the level of dopamine (DA) metabolite dihydroxyphenylacetic acid (DOPAC) and with a reduction of DOPAC/DA and homovanillic acid (HVA)/DA ratios. An assay of adult offspring brain revealed that the prenatal PCPA produced different effects on monoamines in the studied brain structures. The relationships between behavioral abnormalities and alterations in brain monoamine levels consequent on the prenatal PCPA treatment are discussed.

Behavioral alteration in the adult rats prenatally exposed to para-chlorophenylalanine.

In the present work, effects of maternal administration of para-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor, on behavior of adult offspring were studied. Pregnant rats were injected intraperitoneally with PCPA (200/100/100/50 mg/kg) either on the gestational days (GD) 8-11 or 14-17, or with vehicle at the same days. Behavioral parameters, in an open field, the Porsolt forced swim test and the Morris water maze test were evaluated at the age of 3-3.5 months in the male and female offspring. The prenatal PCPA increased activity in an open field in the offspring treated on either GD 8-11 or 14-17. The highest levels of the activity were revealed in the male and female offspring treated on GD 14-17. Besides, the PCPA treatment on GD 8-11 or 14-17 facilitated the intersession habituation of activity to repeated exposures to an open field in the male offspring. Both male and female offspring treated on GD 14-17 showed an increased immobility in the Porsolt forced swim test and a significant learning impairment in the Morris water maze. Thus, it has been shown that administration of PCPA to pregnant rats might cause significant changes in the adult offspring behavior. These results provide further evidence that unfavorable influence may have more adverse effects on the behavioral development of rats when exposed during the final trimester of pregnancy than during the second trimester.