EFFECT OF DOSAGE AND TIMING OF ADMINISTRATION OF NALOXONE ON OUTCOME IN THE RAT VENTRAL COMPRESSION MODEL OF SPINAL-CORD INJURY

The effect of the dosage and timing of administration of naloxone after spinal cord injury in rats via the ventral compression technique is presented. The rat ventral compression technique allows for a ventral compression of the spinal cord without the requirement of a previous laminectomy. It therefore facilitates the creation of an experimental lesion that is similar to that observed in the human clinicopathological situation. The first part of the two-part study presented herein involved the determination of the optimal dose of naloxone, administered intraperitoneally 45 minutes after the creation of the lesion. Of the groups studied (control group through 10.0 mg/kg group), 2.0 mg/kg of naloxone proved to be superior to both lesser and greater dosages. The second part of the study involved the administration of a 2.0 mg/kg dose of naloxone at varying intervals ranging from 10 minutes before lesioning to 24 hours after lesioning. A multiphasic response was again demonstrated, with an optimal time of administration occurring 45 minutes after the creation of the lesion. A significant effect was offered by a midrange dose of naloxone (2.0 mg/kg), administered at 45 minutes after injury (P < 0.02 by analysis of variance and Duncan's multiple range test). These findings are discussed with respect to recent evidence regarding the effects of narcotic antagonists on both mu and kappa narcotic receptors. Past and future experiments must account for these responses to multiphasic dosage and timing of administration.