CISPLATIN-INDUCED NEUROPATHY IN MATURE RATS - EFFECTS OF THE MELANOCORTIN-DERIVED PEPTIDE ORG-2766

A major side effect of cisplatin treatment is peripheral neuropathy. I n the past few years we have provided evidence that the ACTH4-9 analog ue ORG 2766 provides protection against this neuropathy in rats and ma n. In this study we investigated the development of a cisplatin-induce d neuropathy and the protective and therapeutic actions of ORG 2766 in mature rats. We also studied the effects of the peptide and of growth impairment caused by food restriction on nerve conduction velocities in healthy young adult rats (not subjected to any other treatment). In the neuropathy experiment, cisplatin induced a significant decrease i n sensory nerve conduction velocity (SNCV), which could be prevented b y concomitant administration of ORG 2766. The SNCV of the neuropathic animals recovered to control values within 10 weeks of discontinuation of cisplatin treatment. ORG 2766 did not enhance the rate of recovery . In the young adult rats neither ORG 2766 administration nor restrict ed weight gain significantly influenced either the motor or the sensor y nerve conduction velocity. These results validate the animal model o f cisplatin-induced neuropathy.