Trends in Neurosciences
Volume 22, Issue 7, 1 July 1999, Pages 316-320
Journal home page for Trends in Neurosciences

Review
CART peptides: novel addiction- and feeding-related neuropeptides

https://doi.org/10.1016/S0166-2236(98)01377-0Get rights and content

Abstract

CART peptides are novel, putative brain–gut neurotransmitters and co-transmitters that probably have a role in drug abuse, the control of feeding behavior, sensory processing, stress and development. They are abundant, processed and apparently released. Exogenously applied peptides cause inhibition of feeding and have neurotrophic properties. Although the precise sequences, relative abundance and efficacy of all CART peptides are currently being determined, small molecules that are active at putative CART receptors could have substantial therapeutic promise.

Section snippets

Recent history

As mentioned above, CART mRNA was identified in the rat striatum as an mRNA whose levels were increased after administration of cocaine or amphetamine3. While the mRNA was found in other brain areas and tissues, its levels were not changed by psychostimulant-drug administration in those regions. These studies suggested that the products of CART mRNA might be involved in psychostimulant-drug action and, given the presence of CART mRNA in other brain regions, they further suggested that CART

Neuroanatomical studies

Another interesting feature of CART mRNA is that it is highly abundant in the hypothalamus. After hypothalamic-specific cDNAs were produced, the cDNA for CART was found to be highly abundant in this library (in fact it was the third most abundant cDNA found12). In the same study, oxytocin mRNA was found to be the most abundant and vasopressin mRNA the eighth most abundant mRNA species. These results, taken together with others, suggest that CART mRNA or CART peptides are not insignificant in

Physiological actions of CART peptides

The previous studies clearly show that CART peptides are neuronal, but the physiological activity of these peptides remains to be elucidated. This is obviously an important issue and significant positive results have also been found in this area of research.

CART peptides have been found in brain areas that are known to be involved in the physiological control of feeding behavior14, 16. Accordingly, CART-peptide fragments have been examined for their effects on feeding behavior. The fragments

Future studies

It is expected that receptors for CART peptides will soon be identified. This will undoubtedly lead to an intense search for small molecules that could be used as therapeutic agents to mimic or block the endogenous actions of CART peptides. Such pharmacological agents, particularly antagonists, would also be useful for exploring the effects of CART peptides in the brain.

So far, only a few of the physiological effects of CART peptides have been demonstrated. These include effects on feeding

Acknowledgements

The authors acknowledge support from NIH grants RR00165, DA00418 and DA10732, clerical assistance from E. Nadler, and helpful discussions and collaborations with Pastor R. Couceyro, Philip D. Lambert, Ersin O. Koylu, Yoland Smith, Betty Eipper, Dick Mains, Nick Ling and Errol de Souza.

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