Cocaine and amphetamine regulated transcript

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Cocaine and amphetamine regulated transcript (CART) is a neuropeptide which in humans is encoded by the CARTPT gene. CART is an anorexigenic peptide, meaning that it will inhibit feeding when injected in small amounts directly into the brain. It is widely expressed in both the central and peripheral nervous systems, particularly concentrated in the hypothalamus. It appears to have roles in reward, feeding, and stress, and it has the functional properties of an endogenous psychostimulant.

In the arcuate nucleus of the hypothalamus, CART is expressed by virtually all neurones that express pro-opiomelanocortin (POMC), and so is co-localised with the satiety-inducing neuropeptide alpha melanocyte stimulating hormone. These POMC/CART neurones play a key role in the regulation of appetite. They are directly activated in response to leptin, a hormone releasec from adipocytes that circulates in concentrations proportional to total body fat mass. Conversely, they are inhibited by a direct innervation from other arcuate neurones that synthesise the orexogenic neuropetides neuropeptide Y and agouti related peptide, these orexigenic neurones are themselves activated by ghrelin, a hormone secreted from the empty stomach that is potent at stimulating hunger.

CART is also expressed in many other neuronal populations - including by many of the magnocellular oxytocin and vasopressin neurones in the supraoptic nucleus and paraventricular nucleus (PVN) of the hypothalamus. In the rostral hypothalamus, CART neurones are found predominantly in the medial neuroendocrine zone. There are a few CART neurones in the anteroventral periventricular nucleus (AVPV) and in the suprachiasmatic preoptic nucleus; some of these are neuroendocrine, but although the AVPV contains gonadotrophin releasing hormone (GnRH) neurones, these two neuropeptides do not co-localize within the same neurons. More caudally, there is a large population of CART neurons in the periventricular nucleus; virtually all of these are neuroendocrine and about 40% co-localize with somatostatin. ^[1]

In the parvocellular parts of the PVN, CART is expressed by neurons both in areas that contain neuroendocrine cells and in subnuclei containing neurons projecting to preganglionic autonomic cells of the brainstem and spinal cord. The most rostral group of CART cells in the PVN are in the anterior parvicellular PVN and a few of these co-express galanin. In the more central part of the PVN, CART neurones are found in all parvocellular subnuclei. In the most medial aspect of the PVN, CART is extensively co-localized with thyrotrophin releasing hormone, whereas few corticotrophin releasing hormone neurones contain CART. CART is also expressed by neurones in the autonomic parvocellular subcompartments of the PVN — the dorsal parvicellular PVN (dpPVN) and the ventral part of the medial parvicellular PVN (vmpPVN) ^[2] The dpPVN contains mainly preganglionic sympathetic neurons projecting to the intermediolateral cell column in the spinal cord, while the vmpPVN contains most of the preganglionic parasympathetic neurons projecting to the dorsal motor nucleus of the vagus. Parvicellular CART neurons in the vmpPVN also stain for oxytocin.

The largest hypothalamic group of CART neurons is found in the zona incerta and lateral hypothalamic area (LHA). CART co-localizes extensively with melanin-concentrating hormone (MCH) in both of these sites.

A relatively small group of CART-ir neurons is found the dorsomedial hypothalamus in the same area that contains some neuropeptide Y-containing neurones that project to the PVN.

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