Sexual Dimorphic effects in the neurotoxicity induced by MK801 in the rat retrosplenial cortex

DE OLMOS S., BENDER C., DE OLMOS J.S

Pinamar

Congreso; SAN XX annual meeting, PABMBM 10th congress, SAIB XLI annual meeting; 2005

SAN XX annual meeting, PABMBM 10th congress, SAIB XLI annual meeting

NMDA antagonists, like MK-801, are of potential therapeutic benefit for several conditions. However, their ability to produce neurotoxicity and psychosis has hampered their clinical use. A better understanding of these side effects and the mechanism underlying them could result in improving our understanding of psychotic illnesses. To study the mechanism and the extent of the effects produced by this drug we used acute moderate to high doses (5-10 mg/kgr) 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 imunohistochemistry. To further corroborate the sensitivity of these techniques, controls for degeneration with other animal models such as intra-srtiatal injections of quinolinic acid were analysed. 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 analysed both divisions of the granular (RSG) and agranular (RSA) Restrosplenial Cortex. 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 (p < 0.05), SD invaded layer 5 of the immediately neighbouring RSA. Since RSA and RSG have different afferent and efferent connections, it is probable that the sexually dimorphic neuronal toxicity induced by MK-801 is reflected in mechanisms involving sensorial areas which may lead in turn to behavioural differences described in the literature.