Investigation into the effect of d-amphetamine on cisplatin-induced emesis in Suncus murinus

Abstract

Introduction Cocaine- and amphetamine-regulated transcript (CART) peptides are neuropeptides that are implicated in various physiological functions including feeding and emesis. Previous studies in rodents reported that acute administration of amphetamine upregulated the CART mRNA in the striatum. The present study aims to investigate the effect of d-amphetamine on cisplatin-induced emesis in Suncus murinus.

Methods Animals were fasted overnight. On the day of experimentation, animals were injected with d-amphetamine (1, 3 and 10 mg/kg, i.p.) or vehicle (saline, 2 ml/kg, i.p). In another set of experiments, animals were pre-treated with d-amphetamine (10 mg/kg, i.p.) or saline (2 ml/kg, i.p.) 30 min prior to cisplatin (30 mg/kg, i.p.). Food and water intake, emesis, and locomotor activity were assessed for 2 h.

Results D-amphetamine at 10 mg/kg, i.p. inhibited food intake by 83.8% (P < 0.001) within the 2 h observation period. The same dose of d-amphetamine had no effect on water intake but a lower dose (1 mg/kg, i.p.) increased water intake by 78.2% (P < 0.05). D-amphetamine at 1 and 3 mg/kg, i.p., induced emesis in 1 out of 6 animals. When injected at 10 mg/kg, i.p., d-amphetamine induced emesis in 3 out of 6 animals. D-amphetamine also induced a dose-dependent increase in locomotor activity and velocity (P < 0.05). In other experiments, pre-treatment with d-amphetamine (10 mg/kg, i.p.) inhibited food intake by 83.2% compared to saline pre-treated group (P < 0.01). Pre-treatment with d-amphetamine also increased locomotor activity and velocity (P < 0.01). In saline pre-treated group, cisplatin induced 5.3 ± 1.8 episodes of emesis comprises 25.0 ± 7.2 retches and 5.3 ± 1.8 vomits in 7 out of 8 animals. Pre-treatment with d-amphetamine decreased the number of emesis episodes, retches and vomits by 33.3%, 12.0%, and 33.3%, respectively (P > 0.05).

Conclusions These data suggest that d-amphetamine may have differential effects in feeding, emesis and locomotor activity. The studies were supported by a grant from the Research Grants Council of the HKSAR, China (Project no. UGC/FDS11/M07/19).