Anorectic and anxiogenic actions of cocaine– and amphetamine-regulated transcript in the lateral septum

Abstract Cocaine-and amphetamine-regulated transcript (CART) is produced in several brain regions including the hypothalamus where it is made in cells that also produce melanin-concentrating hormone (MCH). MCH+CART cells densely innervate the lateral septum (LS), which integrates food– and mood-related behaviours. However, while MCH typically promotes feeding and anxiolysis, CART suppresses feeding and promotes anxiogenesis. The LS is a target site of the orexigenic actions of MCH, but it is not known if the actions of CART converge or oppose that of MCH in the LS. We implanted a bilateral cannula over the lateral or central LS of male and female wildtype mice and infused vehicle, CART 55–102 , or co-infused CART and MCH. CART did not alter chow intake but suppressed the intake of a palatable high sugar diet in male and female mice, especially when delivered in the medial LS. Furthermore, CART also prevented the orexigenic effect of MCH on palatable feeding intake when infused in the medial LS. We then assessed if CART regulated anxiety-like behaviour via the LS and found that intra-LS CART infusion reduced time spent in the center of an open field in male but not female mice. Our findings indicated that CART elicited anorectic and anxiogenic actions and may function in opposition to or independently of MCH in the LS. These outcomes suggested that putative CART and MCH co-release from MCH neurons may provide biphasic regulation of feeding and anxiety via the LS.