Suppression of autotomy by N-methyl-D-aspartate receptor antagonist (MK-801) in the rat

The effects of different doses and time of administration of the N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801) on the development of the autotomy (self-mutilation) were studied in the rats receiving dorsal root ganglionectomy (DRGn). The rats without any treatment and those treated with normal saline immediately after DRGn were the control groups. Three groups of rats were treated with 0.1, 0.5 or 1.0 mg/kg of MK-801 immediately after DRGn, and another three were treated with 1.0 mg/kg of MK-801 2, 4, or 7 days after DRGn. The behavioral observations of these rats were quantified using an autotomy grading scale ranging from 0 to 19, and the scores were compared among these groups. The rats in the control groups manifested autotomy from 5 to 17 days after DRGn and all of them (100%) attained the highest autotomy score. Lower doses (0.1 or 0.5 mg/kg) of MK-801 had no effect on the development of the autotomy. In contrast, higher dose (1.0 mg/kg) of MK-801 administered immediately after DRGn significantly suppressed the autotomy as compared to the control groups (P < 0.01) and only 17% of the rats in this group attained the highest score. The antagonistic effect was retained when the treatment of MK-801 was delayed to 2 days after DRGn, however, it disappeared when the treatment was delayed to 4 or 7 days after DRGn. Thus, the antagonistic effect of MK-801 on the autotomy induced by DRGn was dose-related and time-dependent. The main role of the NMDA receptor in the development of the autotomy was within several days after DRGn.