SABELUZOLE ADMINISTRATION DOES NOT ENHANCE FAST AXONAL-TRANSPORT IN NORMAL ADULT-RAT SCIATIC-NERVE

Sabeluzole (R58735, Janssen Research Foundation) increased rates of ax onal transport in short term tissue culture experiments and in rats wi th streptozotocin-induced diabetes. The drug was tested for its subacu te (3 days) net effect on axonally transported substances in motor, se nsory, and adrenergic axons of normal adult rats. Sabeluzol was given once daily for 3 days, 1 or 10 mg/kg/day intraperitoneally. Immunofluo rescence was used to identify transported material. Three or 6 hr afte r crushing the sciatic nerves, to interrupt anterograde and retrograde intraaxonal transport, cytofluorimetric scanning was used to quantita te accumulated immunoreactive material. Compared with vehicle treated control rats, no clear differences in the net amounts of accumulated m aterial, or in rates of accumulation, were detected in any axonal type . Since the short-term crush procedure interrupts ongoing axonal trans port, the accumulation pattern reflects the transport characteristics in the crushed axons. The absence of clear increases in transport of s everal substances in this study indicates that sabeluzole did not enha nce net axonal transport above control levels in peripheral axons of n ormal adult rats. Possible reasons for the discrepancy with earlier ob servations on the effect of sabeluzole on fast axonal transport is dis cussed.