A role for the 5-HT1A, 5-HT4 and 5-HT6 receptors in learning and memory

The serotonergic system is implicated in the neurobiological control of learning and memory, both in healthy individuals and pathological disorders, although the underlying mechanisms remain elusive. After the cloning and characterization of serotonin, or 5-hydroxytryptamine (5-HT), receptors and the resultant development of selective agonist and antagonist compounds and transgenic receptor-knockout mice, our understanding of the role of various serotonin receptors in learning and memory has improved. 5-HT1A, 5-HT4 and 5-HT6 receptors are densely expressed in brain regions innervated by serotonergic projections from the raphe nuclei and are associated with learning and memory. Here, we review the evidence that compounds acting on these receptors can have positive effects on learning and memory, and we discuss the potential mechanisms involved. This information raises the possibility that such compounds could be developed as adjunct therapeutics with existing treatments to improve learning and memory deficits, which are core symptoms of Alzheimer's disease, schizophrenia and depression.