Investigating the Role of Serotonin and Ghrelin Receptors in Neurobiology

Drug addiction remains a significant problem worldwide. A new treatment strategy is needed based on the lack of approved pharmacological treatment. Serotonin (5-hydroxytryptamine, 5-HT) receptors have been implicated in a wide variety of physiological functions both in the central nerve system (CNS) and in the periphery. Our research program has been focused on the control and balance of 5-HT2AR and 5-HT2CR systems. It has been shown that these two receptors are in oppositional control with 5-HT2AR antagonists and 5-HT2CR agonists exerting similar effects on behaviors such as impulse control and reactivity to cues. The existence of the homo and heterodimers of 5-HT2AR with 5-HT2CR may play a role in differentiating signaling in this GPCR system. Accumulating data also indicate that function cross-talk between 5-HT2CR and GHS-R1a (growth hormone secretagogue receptor), and the interaction between 5-HT2CR and GHS-R1a would be a new research field to investigate. Chemistry to access bivalent ligands for the system 5-HT2AR and 5-HT2CR or 5-HT2CR and GHS-R1a, as well as ligands attached to cholesterol and serotonin will be discussed.