SODIUM-AZIDE-INDUCED LEARNING-DEFICITS IN RATS - TIME-COURSE AND CORRESPONDING PATHOLOGY

Systemic administration of sodium azide, a selective inhibitor of the mitochondrial enzyme cytochrome oxidase, has been reported to produce deficits in memory and long-term potentiation (Bennett, Diamond, Stryk er, Parks, & Parker, 1992; Bennett & Rose, 1992). We have further char acterized the memory deficits observed during the period of infusion o f this toxin and have evaluated learning and memory following the term ination of infusions to assess the permanence of deficits. In addition , the brains of sodium-azide-infused rats were examined histologically to evaluate neuropathological changes that might accompany the learni ng deficits. We confirmed the deficit in water-maze acquisition observ ed previously during sodium-azide infusion (Bennett & Rose, 1992) but found that azide-infused animals were as capable as vehicle-infused an imals of remembering the platform location once they had learned it. I n addition, during sodium-azide infusion, we found a short-term passiv e-avoidance retention deficit that slowly improved with longer delays. Sodium-azide-infused animals showed deficits in water-maze reversal r etention shortly after the infusion was terminated, but they recovered by 6 months postinfusion. No significant locomotor differences were d etected between azide- and vehicle-infused animals, but a significant fine sensorimotor deficit was detected during azide infusion. Histolog ical analyses revealed no obvious neuronal cell loss after sodium-azid e infusion, but rather a loss of myelinated fiber staining in the retr osplenial (posterior cingulate) cortex. The sodium-azide-infused rat m ay thus serve as an animal model of learning deficits resulting from m etabolic and structural alterations in the Limbic cortex.