Abstract

recorded from 12 rats 10 hrs after cisplatin (5 mg/kg). Basal firings increased to 9.5±3.5 impulses/20s. 12/45 neurons responded to SP. SP 5 and 10 μg/kg increased firings to 27 ± 4, and 64±7 impulses/20 s, respectively. 7/12 SP sensitive neurons also responded to 5HT. Luminal perfusion of 10-7M increased firings to 17±3 impulses/20 s. Combined 10-7M 5-HT and 5, 10 μg/kg of SP enhanced neuronal firings to 60 ± 5, and 133±11 impulses/ 20 s, respectively. Western blot studies demonstrated a 1.1 fold increase in NK1 receptor expression but no change in 5HT3 receptor in the NG 10 hrs following cisplatin. Similar increase in vagal NK1 receptor expression was observed with perfusion of 5-HT (10-5M) for 5 hrs. Administration PCPA, a 5-HT synthesis inhibitor suppressed cisplatin-induced increased in NK1 receptor and completely abolished the enhanced neuronal responses to SP. Conclusion: Anti-cancer therapy with cisplatin causes plastic changes in the NG characterized by upregulation of NK1 receptor in the vagal NG. This is mediated by the 5-HT pathways. Enhanced activation of NK1 receptor in the vagal afferent neurons and its interaction with 5-HT appear to be responsible for the delay emesis observed in anti-cancer chemotherapy.

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