INVESTIGADORES
BENDER Crhistian Luis
congresos y reuniones científicas
Título:
Neurotoxicity Induced by the Noncompetitive Antagonist of the N-Methyl-D-Aspartate Receptor (NMDA) MK-801 in the Rat Retrosplenial Cortex: A Study of Sexual Dimorphic Effects
Autor/es:
DE OLMOS S; BENDER C; DE OLMOS J
Reunión:
Congreso; NIDA International Forum: International Trends and Needs in Drug Abuse Research; 2006
Resumen:
Noncompetitive antagonists of the N-methyl-D-aspartate receptor (NMDA), like phencyclidine, MK-801 and ketamine are classified as dissociative anesthetics, with MK-801 being the most potent of this group. Several studies show that they are of potential therapeutic benefit for several conditions, such as treatment of ischemic brain injury. However, they have limited clinical use due to their ability to induce psychotomimetic effects in humans. In rats, it has been found that under certain conditions they can eventually lead to neurotoxicity. On the other hand, these compounds are also drugs of abuse that induce hallucinations and addiction. Therefore it is important to elucidate how these side effects and the mechanism underlying them are produced. These studies could result in improving our understanding of psychotic illnesses such as schizophrenia. In this work, we studied the extent of the effects produced by MK-801, using acute moderate to high doses (5-10 mg/kg) in male and female rats, and compared different protocols for detecting degeneration, such as the Amino Cupric Silver Technique (A-CuAg), Fluoro Jade B and GFAP immunohistochemistry. Comparing the results obtained by the A-CuAg with the other protocols, it is concluded that A-CuAg was the most sensitive protocol for the detection and accurate appraisal of the neuronal degeneration produced. Thereby, we analyzed both divisions of the granular (RSG) and agranular (RSA) Restrosplenial Cortex, areas that previous reports have shown to be sensitive to the effects of this drug. The somatodendritic degeneration (SD) induced by MK-801 in the female rat was almost completely restricted to layer 4 and 5 of the RSG, instead in the male, besides showing much less cell damage