Effect of early life stress on serotonin responses in the hippocampus of young adult rats

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Abstract
In this study, we investigated the effects of early life stress on several aspects of serotonin (5‐HT) transmission in hippocampus, later on in life. Three‐day‐old rats were subjected to 24‐hour maternal deprivation or control treatment. Maternal deprivation is known to activate the hypothalamo‐pituitary‐adrenal axis, resulting in increased corticosterone levels at a time‐point in life when the axis is particularly insensitive to most stressful stimuli. When these animals had matured to 3 months of age, functional responses to 5‐HT as well as 5‐HT1A‐receptor mRNA expression were examined. Also, indices for hypothalamo‐pituitary‐adrenal function were studied in the adult state, including hippocampal mRNA expression for the mineralocorticoid and the glucocorticoid receptor. Resting membrane potential of CA1 pyramidal neurons was significantly depolarized in animals earlier subjected to maternal deprivation compared to the controls. Despite this depolarized resting potential, hyperpolarizing responses induced by 5‐HT in CA1 pyramidal neurons from deprived compared to non‐deprived rats were attenuated. This attenuation in 5‐HT response was not accompanied by changes in mRNA expression of the 5‐HT1A‐receptor. Maternal deprivation was not found to change any of the neuroendocrine parameters investigated once animals had matured. We conclude that maternal deprivation can alter specific aspects of hippocampal 5‐HT transmission later on in life, possibly by post‐translational modification of the 5‐HT1A‐receptor or changes in the 5‐HT1A‐receptor signal transduction pathway. Synapse 53:11–19, 2004.