Role of serotonin in memory impairment

As a result of its presence in various structures of the central nervous system serotonin (5-HT) plays a role in a great variety of behaviours such as food intake, activity rythms, sexual behaviour and emotional states. Despite this lack of functional specialization, the serotonergic system plays a significant role in learning and memory, in particular by interacting with the cholinergic, glutamatergic, dopaminergic or GABAergic systems. Its action is mediated via specific receptors located in crucial brain structures involved in these functions, primarily the septohippocampal complex and the nucleus basalis magnocellularis (NBM)-frontal cortex. Converging evidence suggests that the administration of 5-HT2A/2C or 5-HT4 receptor agonists or 5-HT1A or 5HT3 and 5-HT1B receptor antagonists prevents memory impairment and facilitates learning in situations involving a high cognitive demand. In contrast, antagonists for 5-HTZ2A/2C and 5-HT4, or agonists for 5-HT1A or 5-HT3 and 5-HT1B generally have opposite effects. A better understanding of the role played by these and other serotonin receptor subtypes in learning and memory is likely to result from the recent availability of highly specific ligands, such as 5-HT1A, 5-HT1B, 5-HT2A receptor antagonists, and new molecular tools, such as gene knock-out mice, especially inducible mice in which a specific genetic alteration can be restricted both temporally and anatomically.