5-HT7 receptors in the modulation of cognitive processes

The abundance of serotonin (5-HT) in the central nervous system can explain its role in the regulation of various functions, such as sleep, feeding,sexuality, emotional status, and pain. In addition, 5-HT localized in “cognitive pathways” with hippocampus and frontal cortex as the main target structures, is involved in learning and memory processes. Recent studies led to the discovery of various types and subtypes of receptors, differentially associated to cognitive mechanisms. Abundant data available reveals that the administration of 5-HT2A/2C and 5-HT4 receptor agonists, or 5-HT1A,5-HT3 and 5-HT1B antagonists improves memory and has a facilitatory effect on learning in situations involving a high cognitive demand. On the contrary 5-HT2A/2C and 5-HT4 receptors antagonists, or 5-HT1A, 5-HT3 and 5-HT1B receptors agonists have opposite effects. Although these results are contradictory, or even opposite, it is important to take into account the effect of global, and unspecific, stimulation of serotonergic receptors and the activation of other neurotransmission systems, together with the type of task used, the way it is administered and the ligand affinity. The aim of this review is to clarify the behavioral role of the recently discovered 5-HT7-type receptor and highlight its involvement in the modulation of learning and memory processes, thus providing a basis to obtain new therapeutic agents and strategies for the treatment of learning and memory disorders.