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

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). CART-expressing MCH 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 orexigenic MCH actions, 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 medial LS of male and female wildtype mice and infused vehicle, CART_55-102, MCH, or CART + MCH. We then assessed the intake of a standard chow diet or palatable high sugar diet over 4 h, as well as anxiety-like behaviour via the open-field test. In both male and female mice, intra-LS CART infusion alone did not produce anorexigenic effects. However, CART infusion diminished MCH-mediated feeding, especially via the lateral LS. By contrast, intra-LS CART infusion reduced time spent in the centre of an open field in male but not female mice. Our findings indicated that CART elicited anorectic effects in the presence of MCH, but CART independently produced anxiogenic effects. These outcomes suggested that putative CART and MCH co-release from MCH neurons may provide biphasic regulation of feeding and anxiety.