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 KCl and 5-hydroxytryptamine (5-HT)-induced depolarization in the rat isolated cervical vagus nerve was investigated using the 'grease gap' extracellular recording technique. KCl (10 mM) perfused onto the isolated nerve previously incubated for 2 h in 10 microM cisplatin initiated a d.c. potential of 1.06 +/- 0.09 mV compared to a potential of 1.29 +/- 0.13 mV in control nerves. Perfusion with 5 microM 5-HT produced a markedly reduced depolarization (0.23 +/- 0.02 mV) in cisplatin-treated nerves compared with control nerves (0.42 +/- 0.04 mV, P = 0.005). This effect was enhanced when 5-HT was reapplied 30 min later (0.19 +/- 0.02 mV in cisplatin-treated 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 significantly (P = 0.004) reduced by the addition of dexamethasone (10 microM) to the incubation buffer (0.34 +/- 0.04 mV). These results are discussed in the light of the emetic and neurotoxic effects of cisplatin and the protective effects of dexamethasone.