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Lack of long-term behavioral alterations after early postnatal treatment with tropisetron: implications for
Dragos Inta1, Miriam A Vogt, Juan M Lima-Ojeda
1Department for Psychiatry and Psychotherapy, RG Animal Models in Psychiatry, Central Institute of Mental Health Mannheim, University of Heidelberg, J5, 68159 Mannheim, Germany. Dragos.Inta@zi-mannheim.de
Insights
Early postnatal exposure to tropisetron did not cause long-term behavioral changes in mice. This study investigated potential cognitive, schizophrenia-like, and emotional effects following early-life tropisetron administration.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- The early postnatal period is crucial for brain development.
- Cajal-Retzius cells in the cortex regulate neuronal migration and maturation.
- Tropisetron, acting on 5-HT(3) receptors, can disrupt cortical column formation during perinatal stages, potentially linking to neuropsychiatric disorders.
Purpose of the Study:
- To investigate the long-term behavioral consequences of early postnatal exposure to tropisetron.
- To assess potential cognitive, schizophrenia-like, and emotional deficits in mice treated with tropisetron during a critical developmental window.
Main Methods:
- Administration of tropisetron (1mg/kg, i.p.) to mice from postnatal days 2-12.
- Evaluation of behavioral alterations using multiple established assays.
- Comparison of tropisetron-treated group with control animals.
Main Results:
- No significant long-term cognitive alterations were observed.
- No significant schizophrenia-like behavioral changes were detected.
- No significant emotional alterations were found in tropisetron-exposed mice compared to controls.
Conclusions:
- Early postnatal exposure to tropisetron in mice does not appear to induce lasting behavioral deficits.
- These findings suggest that tropisetron may not cause protracted deleterious neuropsychiatric effects when administered during early life stages.
- Further research may explore the precise mechanisms and potential nuances of tropisetron's impact on developing brains.
Abstract:
The early postnatal period represents a critical time window for brain development. Transient Cajal-Retzius cells in layer I of the cortex play an important role in cortical lamination by modulating neuronal migration and maturation. Recent data have demonstrated that the 5-HT(3) receptor antagonist and alpha7 nicotinic receptor partial agonist tropisetron, acting via 5-HT(3) receptors expressed on Cajal-Retzius cells, can disturb the formation of cortical columns at perinatal stages. This process is thought to be involved in several neuropsychiatric disorders. Here we investigated the possible long-term behavioral effects of exposure to tropisetron at early postnatal stages in mice. We found that the administration of 1mg/kg, intraperitoneal (i.p.) tropisetron from postnatal days 2-12 (P2-P12) did not induce significant cognitive, schizophrenia-like or emotional alterations in tropisetron-treated animals as compared to controls, when tested in multiple behavioral assays. These results may be of relevance regarding the possible protracted deleterious neuropsychiatric effects of tropisetron during early life.
