Pharmacology of sigma (σ) receptor ligands from a behavioral perspective

The σ receptors are regarded as unique binding sites, distinct from opiate and PCP receptors and implicated in higher brain function. They were classified into σl and σ2 subtypes, the former was cloned from rodent and human tissues while the latter has not yet been fully characterized. Although the precise mechanism of the functional response of σ receptors is still uncertain, it has been accepted that they can modulate a number of central neurotransmitter systems, including glutamate/NMDA, serotonergic, dopaminergic, noradrenergic routes, as well as some other signaling pathways (e.g. neurotrophin and growth factor signaling) which are seemingly important for the brain function. In accordance with their modulatory role, σ receptor ligands have been proposed to be useful in several therapeutic areas such as schizophrenia, depression and anxiety, amnesic and cognitive deficits, drugs of abuse. The present review summarizes the findings related to the pharmacological effects and potential activity of σ receptor ligands from behavioral models predictive of some neuropsychiatric disorders.