CISPLATIN ACUTELY REDUCES 5-HYDROXYTRYPTAMINE-INDUCED VAGAL DEPOLARIZATION IN THE RAT - PROTECTIVE ACTION OF DEXAMETHASONE

The effect of the anti-cancer cytotoxic drug cisplatin on KCI and 5-hy droxytryptamine (5-HT)-induced depolarization in the rat isolated cerv ical vagus nerve was investigated using the 'grease gap' extracellular recording technique. KCl (10 mM) perfused onto the isolated nerve pre viously incubated for 2 h in 10 mu M cisplatin initiated a d.c. potent ial of 1.06+/-0.09 mV compared to a potential of 1.29+/-0.13 mV in con trol nerves. Perfusion with 5 mu M 5-HT produced a markedly reduced de polarization (0.23+/-0.02 mV) in cisplatin-treated nerves compared wit h control nerves (0.42+/-0.04 mV, P=0.005). This effect was enhanced w hen 5-HT was reapplied 30 min later (0.19+/-0.02 mV in cisplatin-treat ed compared with 0.42+/-0.03 mV in controls, P<0.0001). The inhibitory effect of cisplatin on 5-HT-induced depolarization was found to be si gnificantly (P=0.004) reduced by the addition of dexamethasone (10 mu M) to the incubation buffer (0.34+/-0.04 mV). These results are discus sed in the light of the emetic and neurotoxic effects of cisplatin and the protective effects of dexamethasone.