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Published on: December 14, 2014
Maternal para-chlorophenylalanine exposure modifies central monoamines and behaviors in the adult offspring
Ludmila A Vataeva1, Vladimir S Kudrin, Elena A Vershinina
1Laboratory of Ontogenesis of the Nervous System, Pavlov Institute of Physiology of the Russian Academy of Sciences, Nab. Makarova, 6, St. Petersburg 199034, Russia. vataeva@yandex.ru
Insights
Prenatal exposure to para-chlorophenylalanine (PCPA) in rats models neurodevelopmental disorders by altering serotonin levels. This exposure reduced anxiety and neophobia, impacting dopamine metabolites in the fetal brain.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Prenatal exposure to para-chlorophenylalanine (PCPA), a serotonin synthesis inhibitor, creates a rat model for neurodevelopmental disorders.
- Previous studies showed PCPA exposure leads to fetal serotonin depletion, altered open field activity, depression-related behaviors, and spatial learning impairments in offspring.
Purpose of the Study:
- To investigate the effects of prenatal PCPA exposure on anxiety-related behavior, neophobia, and hedonic responses in adult offspring.
- To examine the impact of PCPA on monoamine levels, specifically dopamine (DA) and its metabolites, in the fetal and adult offspring brain.
- To assess the effect of a selective serotonin reuptake inhibitor (SSRI), paroxetine, on locomotor activity in PCPA-exposed offspring.
Main Methods:
- Rats were prenatally exposed to PCPA.
- Behavioral tests included elevated plus-maze, novel environment fluid intake, and saccharin preference tests.
- Locomotor activity was assessed in the open field test.
- Monoamine levels (serotonin, dopamine, DOPAC, HVA) were measured in fetal and adult brains using biochemical assays.
- Paroxetine was administered to assess its effect on locomotor activity.
Main Results:
- Prenatal PCPA exposure significantly reduced anxiety-related behavior and neophobia in offspring.
- Offspring exhibited increased saccharin preference, indicating hedonic changes.
- Confirmed earlier findings of altered open field locomotor activity.
- Paroxetine administration decreased locomotor activity in PCPA-treated offspring.
- Fetal PCPA exposure led to decreased dopamine metabolite DOPAC and altered DOPAC/DA and HVA/DA ratios.
- Prenatal PCPA exposure differentially affected monoamine levels in various brain structures of adult offspring.
Conclusions:
- Prenatal PCPA exposure in rats provides a valuable model for studying neurodevelopmental disorders.
- The model demonstrates significant alterations in anxiety, neophobia, and hedonic responses, linked to changes in brain monoamine systems.
- Findings highlight the complex interplay between serotonin and dopamine pathways in neurodevelopment and behavior.
Abstract:
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.
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