FIGURE 2.

Acute administration of REL-1017 did not cause Olney lesions in the brain cingulate cortex. (A) histological examination of the cingulate cortex, one of the brain regions which are most vulnerable to the neurotoxic effect of acute NMDA receptor antagonism. Black arrow marks indicate the presence of the neuronal vacuolations, which are the microscopic features of Olney’s lesions, in the brains of animals treated with MK-801 (positive control). (B) To statistically compare differences between treatment groups, we have quantified the number and scored a grade of Olney’s lesion severity. This analysis confirmed that oral gavage administration of REL-1017 in all tested doses to both male and female prague-Dawley rats did not produce Olney’s lesions. Compared to REL-1017, the effect of MK-801 on cortical neurons was statistically significantly different (p < 0.0001). Also, the oral administration of methadone racemate to both male and female Sprague-Dawley rats did not produce Olney’s lesions.