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  • Review Article
  • Published:

CART peptides: regulators of body weight, reward and other functions

Nature Reviews Neuroscience volume 9, pages 747–758 (2008)Cite this article

A Corrigendum to this article was published on 01 March 2010

Key Points

  • The CART (cocaine- and amphetamine-regulated transcript) gene, transcripts and peptides were discovered through the initial observation that psychostimulant drugs elevated the levels of the CART mRNA. Although the full name reflects this particular effect, CART peptides are involved in more processes than just those that mediate the effects of drugs like cocaine.

  • CART mRNA is transcribed by the action of known transcription factors, such as cyclic AMP-response-element-binding protein (CREB), and the CART propeptide is processed into smaller active fragments by prohormone convertases.

  • CART peptides are neurotransmitters and neurohormones that are widely but discretely distributed throughout the brain and the periphery.

  • The CART peptide receptor (although it is possible that there is more than one) is thought to be a G-protein-coupled receptor that signals through inhibitory (Gi/o) mechanisms.

  • There has been much interest in CART peptides as regulators of body weight. Evidence for this role comes from both animal and human studies.

  • CART peptides, when injected into the nucleus accumbens, reduce the actions of psychostimulant drugs like cocaine. It has been proposed that CART peptides modulate the effects of cocaine.

  • Many experiments suggest that CART peptides also play a part in endocrine regulation, stress, anxiety and depression, cardiovascular function, pain and other processes.

  • Because CART peptides have so many effects, including a major role in body weight regulation, the CART system could be an interesting target for drug development.

Abstract

Over the past decade or so, CART (cocaine- and amphetamine-regulated transcript) peptides have emerged as major neurotransmitters and hormones. CART peptides are widely distributed in the CNS and are involved in regulating many processes, including food intake and the maintenance of body weight, reward and endocrine functions. Recent studies have produced a wealth of information about the location, regulation, processing and functions of CART peptides, but additional studies aimed at elucidating the physiological effects of the peptides and at characterizing the CART receptor(s) are needed to take advantage of possible therapeutic applications.

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Figure 1: Amino-acid sequences of rat proCART and CART peptides.
Figure 2: Proposed CART receptor signalling.
Figure 3: Effects of a missense mutation resulting in Leu34Phe in proCART.
Figure 4: CART peptides as potential regulators of dopamine activity in the nucleus accumbens.
Figure 5: The involvement of the CART system in the stress response.

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Acknowledgements

The authors acknowledge the helpful suggestions of Drs Nestler, Hunter, Sundler, Wierup and Vrang, and the support of the US National Institutes of Health.

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  1. Neuroscience Division, Yerkes National Primate Research Center of Emory University, 954 Gatewood Road NE, Atlanta, 30329, Georgia, USA

    G. Rogge, D. Jones, G. W. Hubert, Y. Lin & M. J. Kuhar

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G. Rogge, D. Jones, G. W. Hubert, Y. Lin and M. J. Kuhar

CART peptides: regulators of body weight, reward and other functions. Nature Reviews Neuroscience 9, 747–758 (2008); doi:10.1038/nrn2493

Michael Kuhar received some funding from Pfizer Inc. for 2007.

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Glossary

Intracisternal injection

The injection of a substance into the space between the cerebellum and the medulla, which is filled with cerebrospinal fluid.

Tyrosine hydroxylase

The enzyme that catalyzes the conversion of L-tyrosine to dihydroxyphenylalanine (DOPA), which is a precursor of dopamine.

Elevated plus maze

A test that is used to assess anxiety-like behaviour in animals, usually rats or mice. The basic measure is the animal's preference — measured as duration of inhabitation — for dark, enclosed places over bright, more open places. More time spent in the bright and open areas suggests a lower level of anxiety.

Formalin test

A model of chronic pain that is usually carried out in rats or mice as a test for substances that reduce pain. It involves a subcutaneous injection of formalin into the hind paw, which causes severe inflammation. The pain measurement can be the time the animal spends with weight on the injected paw or the time the animal spends biting and licking the injected paw.

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Rogge, G., Jones, D., Hubert, G. et al. CART peptides: regulators of body weight, reward and other functions. Nat Rev Neurosci 9, 747–758 (2008). https://doi.org/10.1038/nrn2493

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