CART (
cocaine- and
amphetamine-regulated transcript)
peptides are
neuromodulators that are involved in feeding,
drug reward, stress, cardiovascular function, and bone remodeling. CART
peptides are abundant but discretely distributed in the brain, pituitary and adrenal glands, pancreas, and gut. High expression of CART in discrete hypothalamic nuclei associated with feeding has led to behavioral and pharmacological studies that strongly support an
anorectic action of CART in feeding. Subsequent studies on humans and transgenic animals provide additional evidence that CART is important in the regulation of appetite as mutations in the CART gene are linked to
eating disorders, including
obesity and
anorexia. The expression of CART in the mesolimbic
dopamine circuit has lead to functional studies demonstrating CART's psychostimulant-like effects on locomotor activity and conditioned place preference in rats. These and other findings demonstrated that CART modulates mesolimbic
dopamine systems and affects psychostimulant-induced reward and reinforcing behaviors. The link between CART and psychostimulants was substantiated by demonstrating alterations of the CART system in human
cocaine addicts. CART seems to regulate the mesolimbic
dopamine system, which serves as a common mechanism of action for both feeding and addiction. Indeed, recent studies that demonstrated CART projections from specific hypothalamic areas associated with feeding to specific mesolimbic areas linked to reward/motivation behaviors provide evidence that CART may be an important connection between food- and
drug-related rewards. Given the enormous public health burden of both
obesity and
drug addiction, future studies exploring the
pharmacotherapies targeting
CART peptide represent an exciting and challenging research area.