EP-007 - CENTRAL ADMINISTRATION OF COCAINE- AND AMPHETAMINE-REGULATED TRANSCRIPT PEPTIDE REDUCES CISPLATIN-INDUCED EMESIS AND C-FOS EXPRESSION IN SUNCUS MURINUS.

S. Chan¹, Z. Lu², B. Jiang¹, D. Cui², I. Sakata³, T. Sakai³, H. Wong², T. Chan², J. Rudd²; ¹Caritas Institute of Higher Education, Hong Kong SAR, China, ²The Chinese University of Hong Kong, Hong Kong SAR, China, ³Saitama University, Saitama, Japan.

Background: Cocaine- and amphetamine-regulated transcript (CART) peptides are important modulators that are expressed in the brain and contribute to various physiological functions. The present study examined if centrally administered CART peptide modulates cisplatin-induced emesis and c-Fos expression in S. murinus.

Methods: Animals were anaesthetized with 3% isoflurane and then stereotaxically implanted with a guide cannula into the lateral ventricle and allowed a 7-day recovery before further experimentation. After overnight fasting, animals were pre-treated with CART (55-102) (0.1 nmol, i.c.v.) or saline (5 µl, i.c.v.) 30 min prior to cisplatin (30 mg/kg, i.p.) or saline (10 ml/kg). Behaviour was assessed for 2 h and brain tissues were then collected for c-Fos immunohistochemistry.

Results: Administration of saline or CART (55-102) did not induce emesis during the pre-treatment period. However CART (55-102) subsequently reduced the number of retches induced by cisplatin by 42 % (P < 0.05, n = 11-12). CART (55-102) alone induced c-Fos expression in the nucleus tractus solitarius, lateral hypothalamus, paraventricular hypothalamus, and bed nucleus of the stria terminalis (BNST), compared to saline-treated animals (P < 0.05). Cisplatin induced c-Fos expression in all these areas and also in the area postrema (AP), arcuate nucleus, and central nucleus of the hypothalamus (P < 0.01). Pre-treatment with CART (55-102) significantly attenuated cisplatin-induced c-Fos expression in the BNST and AP (P < 0.05).

Conclusion: The action of CART (55-102) to attenuate cisplatin-induced emesis may involve both the forebrain limbic system and the brainstem in S. murinus. The studies were supported by a grant from the Research Grants Council of the HKSAR, China (Project no. UGC/FDS11/M07/19).