Effects of sigma receptor ligands on psychiatric disorders

It has recently been suggested that sigma receptors are involved in psychiatric disorders. Sigma₁ receptor antagonists are effective in animal models of positive symptoms, cognitive deficit and disruption of prepulse inhibition in schizophrenia. They also inhibit the development and expression of the conditioned place preference induced by cocaine. On the other hand, sigma₁ receptor agonists reduce the immobility time in the forced swimming and tail suspension tests. Furthermore, sigma₁ receptor agonists attenuate the conditioned fear stress (CFS) response (which is not attenuated by typical anxiolytics or antidepressants) in rodents. The attenuating effects are mediated through sigma₁ receptors, which are closely related to the mesolimbic dopaminergic systems. Sigma₁ receptor agonists also have anti-amnesic effects in various experimental models. Neurosteroids such as dehydroepiandrosterone sulfate and pregnenolone sulfate attenuate the CFS response and have anti-amnesic effects, the effects being mediated via sigma₁ receptors. These findings suggest that sigma receptors are novel potential targets for the treatment of psychiatric disorders such as schizophrenia, drug abuse, depression and dementia.