Methamphetamine exposure during the preweaning period alters hippocampal neurogenesis

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Abstract

Background: Methamphetamine (MA) is one of the most abused illicit drugs in the world. Abuse of this drug among adolescents, given the still-developing physiological functions of the body, including the central nervous system (CNS), is problematic. The hippocampus (HP) is part of the limbic system and is associated with cognition, as well as the reward system, which is mediated by dopamine (DA). Disruption of this system is the primary mechanism underlying addiction and results in cognition deficiencies. Methods: In this work, we focused on the influence of MA on the development of the rat HP during postnatal days 11–20. Subsequently, after MA application, we studied learning and memory processes using the Morris Water Maze (MWM). After the MWM, we measured the expression of the protein doublecortin (DCX), neurotransmitter levels of DA, GLU, 5HT, NA, and GABA, and glial fibrillary acidic protein (GFAP). Results: MA significantly impairs HP neurogenesis when administered during the third postnatal week, as indicated by reduced expression of DCX, which correlates with increased levels of glial fibrillary acidic protein (GFAP), but these changes were not significantly reflected in learning abilities and memory formation nor the levels of neurotransmitters. Conclusion: We speculate that these mechanisms must be strongly expressed on multiple molecular levels to be able to cause cognitive changes. A significant role in this process is associated with the ability of young organisms to compensate and, to a certain extent, neurotoxic effects.

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