Involvement of neurosteroids in normal and pathological behaviour

Introduction. The nervous system synthesises steroids (then called neurosteroids) de novo from cholesterol. These substances play a role in a number of functions related to the allosteric modulation of the main ionotropic receptors in the central nervous system (CNS). Aim. To describe the most important behavioural and cognitive processes in which neurosteroids are involved and which can open up new perspectives for research focused above all on their possible therapeutic use in pathologies affecting the CNS, such as the cognitive impairment associated to neurodegenerative diseases, addictions like alcoholism, anxiety disorders, and epilepsy and convulsive behaviour. Development. We provide a brief outline of the concept of neurosteroids, their synthesis, how they act on receptors for neurotransmitters and their distribution throughout nerve tissue. We then offer an extensive, up-to-date, critical review of the main psychological processes that they are involved in. Conclusions. Neurosteroids offer an important therapeutic potential. In epileptiform behaviour, no tolerance is developed to the anticonvulsive effects of these substances with repeated administration, unlike the case of benzodiazepines, although the study of synthetic analogues and agents that step up the synthesis of neurosteroids in the CNS seems to be decisive owing to the limitation imposed by the long-term systemic use of hormones. In anxiety disorders, they offer several advantages that are comparable to the prototypical anxiolytic agents, that is, benzodiazepines, but also their chief side effects, such as sedation. In cognitive impairment, the enormous potential for cognitive enhancement in animal models is not reproduced in humans with dementia, although controlled clinical trials are needed to evaluate the benefits and risks of replacement therapy with steroids. © 2007, Revista de Neurología.