Open Access Research article

Synergistic effect of CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin on food intake regulation in lean mice

Lenka Maletínská1, Jana Maixnerová1, Resha Matyšková1, Renata Haugvicová2, Zdeno Pirník3, Alexander Kiss3 and Blanka Železná1*

Author Affiliations

1 Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Prague 6, Czech Republic

2 Institute of Microbiology, Academy of Sciences of the Czech Republic, Vídeňská 1083, 14200 Prague 4, Czech Republic

3 Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlárska 3, 83306 Bratislava, Slovak Republic

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BMC Neuroscience 2008, 9:101  doi:10.1186/1471-2202-9-101

Published: 21 October 2008

Abstract

Background

CART (cocaine- and amphetamine-regulated transcript) peptide and cholecystokinin (CCK) are neuromodulators involved in feeding behavior. This study is based on previously found synergistic effect of leptin and CCK on food intake and our hypothesis on a co-operation of the CART peptide and CCK in food intake regulation and Fos activation in their common targets, the nucleus tractus solitarii of the brainstem (NTS), the paraventricular nucleus (PVN), and the dorsomedial nucleus (DMH) of the hypothalamus.

Results

In fasted C57BL/6 mice, the anorexigenic effect of CART(61-102) in the doses of 0.1 or 0.5 μg/mouse was significantly enhanced by low doses of CCK-8 of 0.4 or 4 μg/kg, while 1 mg/kg dose of CCK-A receptor antagonist devazepide blocked the effect of CART(61-102) on food intake. After simultaneous administration of 0.1 μg/mouse CART(61-102) and of 4 μg/kg of CCK-8, the number of Fos-positive neurons in NTS, PVN, and DMH was significantly higher than after administration of each particular peptide. Besides, CART(61-102) and CCK-8 showed an additive effect on inhibition of the locomotor activity of mice in an open field test.

Conclusion

The synergistic and long-lasting effect of the CART peptide and CCK on food intake and their additive effect on Fos immunoreactivity in their common targets suggest a co-operative action of CART peptide and CCK which could be related to synergistic effect of leptin on CCK satiety.