Sigma (
sigma) receptors, first defined as a subclass of
opioid receptors, later confounded with the high affinity
phencyclidine (PCP) binding sites, now are regarded as unique binding sites, distinct from
opiate and
PCP receptors, and related to higher brain function. The investigation of functional significance of
sigma receptors in the brain has been hampered for many years by relative lack of specific tool drugs and by the unavailability of their coherent classification into postulated agonists and antagonists. However, a potential involvement of
sigma receptors in
psychotic disorders was first suggested soon after their discovery. The
sigma receptors are classified into two subtypes, sigma (1) and sigma (2) receptors, of which the first was recently cloned from rodent and human tissues while the second has not yet been fully characterized. Although the precise mechanism of the functional response of these receptors is still uncertain, it is accepted that
sigma receptors can modulate a number of central
neurotransmitter systems, including noradrenergic, glutamatergic and dopaminergic ones. The
sigma receptors have been postulated to be involved in numerous pharmacological and physiological functions, including
motor disorders,
psychotic disorders, neuroprotective mechanisms. In the last years, a number of compounds with a high affinity and selectivity for sigma binding sites have been discovered and investigated for their therapeutic potential. In this review, we try to summarize the behavioral effects of
sigma receptor ligands that have been described, and their activity in animal models related to some
brain disorders, especially
schizophrenia and
affective disorders.