Glial reactivity after antipsychotic treatment. An experimental study in rats and its implications for psychiatry.

INTRODUCTION: The importance of the glial cells in the function of the nervous system and in its pathology has been the object of multiple studies in the last years. Specifically, their role in the action of the antipsychotics is debated. Our study has analyzed glial reactivity in rats treated with antipsychotics. METHODOLOGY: In a first ultrastructural study of the arcuate nucleus of the hypothalamus, the animals were treated with chlorpromazine for 40 days, and were sacrificed at the end of the treatment, after 20 days of rest without treatment. In another series of studies, with the light microscope and immunohistochemistry we evaluated the immunoreactivity of the glial fibrillary acidic protein (GFAP) in six regions of the central nervous system of rats treated with typical and atypical antipsychotics. RESULTS: With the electron microscope, the animals treated with chlorpromazine showed a significant reduction of the axosomatic synapses on the neurons of the hypothalamic arcuate nucleus and an increase of glial presence, as noted by the greater amount of astrocyte processes. The mentioned modifications were reversible, tending to normalize in a group of animals sacrificed 20 days after completion of the treatment. In the immunohistochemical study, the glial reaction was important in the territory of the nucleus accumbens with all the antipsychotics, moderate in the cingulate cortex, although only with atypical antipsychotics, and scarcely significant in the rest of the regions. CONCLUSIONS: Our results confirm that the glial cells are targets of the antipsychotic action, and this will allow us to better understand the action of these drugs and the role of the glial cells in the normal function of the nervous system and in the mental disease.

Reactividad glial tras el tratamiemto con antipsicóticos. Estudio experimental en ratas e implicaciones para la psiquiatría / Glial reactivity after antipsychotic treatment. An experimental study in rats and its implications for psychiatry

Introducción. La importancia de las células gliales en la función del sistema nervioso y en su patología ha sido objeto de múltiples estudios en los últimos años. Concretamente se debate su papel en la acción de los antipsicóticos. Nuestro estudio analiza la reactividad glial en ratas tratadas con antipsicóticos. Metodología. En un primer estudio ultraestructural del núcleo arcuato del hipotálamo, los animales fueron tratados con clorpromacina durante 40 días, sacrificándose al final del tratamiento y tras 20 días de descanso. En otra serie de estudios, con el microscopio de luz y con técnicas inmunohistoquímicas valoramos la reacción a la proteína glial fibrilar ácida (GFAP) en seis regiones del sistema nervioso central de ratas tratadas con antipsicóticos típicos y atípicos. Resultados. Con el microscopio electrónico, las ratas tratadas mostraron una reducción significativa de las sinapsis axosomáticas sobre las neuronas del núcleo arcuato del hipotálamo, así como un incremento de la presencia glial evidenciable por la mayor cantidad de laminillas de astrocitos. Las modificaciones mencionadas son reversibles, tendiendo a normalizarse en los animales sacrificados a los 20 días de finalizado el tratamiento. En el estudio inmunohistoquímico la reacción astrocitaria fue muy importante en el territorio del núcleo accumbens con todos los antipsicóticos, moderada en la corteza cingular, aunque sólo con los atípicos, y discreta en el resto de las regiones. Conclusiones. Nuestros resultados confirman que las células gliales son diana de los antipsicóticos, lo que ha de contribuir a entender mejor la acción de estos fármacos y el papel de las células gliales en el normal funcionamiento del sistema nervioso y en la enfermedad mental (AU)

Introduction. The importance of the glial cells in the function of the nervous system and in its pathology has been the object of multiple studies in the last years. Specifically, their role in the action of the antipsychoticsis debated. Our study has analyzed glial reactivity in rats treated with antipsychotics. Methodology. In a first ultrastructural study of the arcuate nucleus of the hypothalamus, the animals were treated with chlorpromazine for 40 days, and were sacrificed at the end of the treatment, after 20 days of rest without treatment. In another series of studies, with the light microscope and immunohistochemistry we evaluated the immunoreactivity of the glial fibrillary acidic protein (GFAP) in six regions of the central nervous system ofrats treated with typical and atypical antipsychotics. Results. With the electron microscope, the animals treated with chlorpromazine showed a significant reduction of the axosomatic synapses on the neurons of the hypothalamic arcuate nucleus and an increase of glial presence, as noted by the greater amount of astrocyte processes. The mentioned modifications were reversible, tending to normalize in a group of animals sacrificed 20 days after completion of the treatment. In the immunohistochemical study, the glial reaction was important in the territory of the nucleus accumbens with all the antipsychotics, moderate in the cingulate cortex, although only with atypical antipsychotics, and scarcely significant in the rest of the regions. Conclusions. Our results confirm that the glial cells are targets of the antipsychotic action, and this will allow us to better understand the action of these drugs and the role of the glial cells in the normal function of the nervous system and in the mental disease (AU)