The role of CART peptide in learning and memory: A potential therapeutic target in memory-related disorders

Cocaine and amphetamine-regulated transcript (CART) mRNA and peptide are vastly expressed in both cortical and subcortical brain areas and are involved in critical cognitive functions. CART peptide (CARTp), described in reward-related brain structures, regulates drug-induced learning and memory, and its role appears specific to psychostimulants. However, many other drugs of abuse, such as alcohol, opiates, nicotine, and caffeine, have been shown to alter the expression levels of CART mRNA and peptides in brain structures directly or indirectly associated with learning and memory processes. However, the number of studies demonstrating the contribution of CARTp in learning and memory is still minimal. Notably, the exact cellular and molecular mechanisms underlying CARTp effects are still unknown. The discoveries that CARTp effects are mediated through a putative G-protein coupled receptor and activation of cellular signaling cascades via NMDA receptor-coupled ERK have enhanced our knowledge about the action of this neuropeptide and allowed us to comprehend better CARTp exact cellular/molecular mechanisms that could mediate drug-induced changes in learning and memory functions. Unfortunately, these efforts have been impeded by the lack of suitable and specific CARTp receptor antagonists. In this review, following a short introduction about CARTp, we report on current knowledge about CART's roles in learning and memory processes and its recently described role in memory-related neurological disorders. We will also discuss the importance of further investigating how CARTp interacts with its receptor(s) and other neurotransmitter systems to influence learning and memory functions. This topic is sure to intrigue and motivate further exploration in the field of neuroscience.