Effects of d-amphetamine and cocaine-and amphetamine-regulated transcript (CART) peptide on cyclophosphamide-induced emesis in Suncus murinus

Abstract

<b>Objective</b>: Cocaine- and amphetamine-regulated transcript (CART) peptide is a neuromodulator implicated in multiple physiological responses. Our previous studies demonstrated that d-amphetamine and CART (55–102) may modulate cisplatin-induced emesis in <i>Suncus murinus</i>. The objective of the present study is to investigate the effect of d-amphetamine and CART (55–102) on cyclophosphamide-induced emesis.

<b>Methods</b>: After overnight fasting, animals were pretreated with d-amphetamine (10 mg/kg, i.p.) or saline (2 mL/kg, i.p.) for 30 min followed by cyclophosphamide (200 mg/kg, i.p.) or saline (2 mL/kg, i.p.). In other studies, animals were anaesthetized with 3% isoflurane and then stereotaxically implanted with a guide cannula into the lateral ventricle and allowed a 7-days recovery before further experimentation. On the day of the experiment, animals were pretreated with CART (55–102) (0.1 nmol, i.c.v.) or saline (5 μL, i.c.v.) for 30 min followed by cyclophosphamide (200 mg/kg, i.p.) or saline (2 ml/kg, i.p.). Behaviour and food and water intake and locomotor activity were then recorded for 2 h.

<b>Results</b>: D-Amphetamine induced emesis in 2 out of 10 animals during the pretreatment period but subsequently failed to affect the cyclophosphamide-induced emetic response, or the associated inhibition of food intake (n = 10, p > 0.05). However, d-amphetamine significantly increased the locomotor activity of animals during the pretreatment period and in the period where animals had been treated with cyclophosphamide (n = 10, p < 0.0001). In other studies, CART (55–102) did not induce emesis alone and it also failed to antagonize cyclophosphamide-induced emesis (n = 9, p > 0.05) and the associated reduction of food intake (92.4 % reduction, n = 9, p < 0.01). CART (55–102) did not increase locomotor activity and it also did not reverse the cyclophosphamide-induced inhibition of water intake.

<b>Conclusions</b>: These data indicate that action of cyclophosphamide to induce emesis and inhibit food intake does not involve the CART system in S. <i>murinus</i>. The differential action of CART (55–102) and d-amphetamine to modulate locomotor activity requires further investigation. The studies were supported by the Institutional Development Grant of Saint Francis University (Project no. IDG220115).