Effects of bilateral olfactory bulbectomy on N-methyl-D-aspartate receptorfunction: Autoradiographic and behavioral studies in the rat

Rat bilateral olfactory bulbectomy (OBX) serves as a useful model in the st udy of depression and the mechanisms of action of antidepressant treatments . Considering the evidence of NMDA receptors involvement in depression, the present study was undertaken in order to investigate the time-course effec ts of OBX on the NMDA receptor function. Following bilateral olfactory bulb ectomy, rats display an increase in locomotor activity and changes in other types of behavior in a novel environment. Autoradiographic experiments usi ng the noncompetitive NMDA antagonist [I-125]-iodo-MK-801 as the labeling a gent showed that this increase in behavioral activities corresponds to a de crease in [I-125]-iodo-MK-801 binding in a number of brain regions. In most regions, this reduction reached significance by the third week following O BX. However, in some cortical areas-a nucleus of the thalamus (AV) and one of the amygdala (LA)-this reduction was already significant in the first or second week following OBX and lasted throughout the 4 weeks of the study. We also compared the behavioral modifications induced by a challenge inject ion of MK-801 (0.2 mg/kg i.p.) in OBX and sham-operated rats. This challeng e is known to induce hyperlocomotion and a number of stereotypies in naive rats. These effects were drastically reduced in OBX as compared to sham-ope rated rats. These data are consistent with the above-mentioned decrease in cerebral binding of MK-801 to NMDA receptors. (C) 2001 Wiley-Liss, Inc.