Behavioural Physiology of Serotonergic and Steroid-Like Anxiolytics as Antistress Drugs

Pharmacological studies are useful tools to understand the neurobiological basis of behavioural and physiological stress mechanisms. Ipsapirone, a 5-HT1A autoreceptor agonist is a representative of novel anxiolytics without the disadvantages of benzodiazepam-like drugs. Behavioural, physiological and neuroendocrine studies in the rat are reviewed which were aimed to investigate the antistress properties of ipsapirone during reexposure to various conditioned emotional stress situations. It is demonstrated that in certain situations, probably due to a stress-induced sensitisation of postsynaptic 5-HT1A receptors, anxiolytic doses of the drug may show prostress (anxiogenic) behavioural and neuroendocrine effects. Furthermore, brain corticosteroid receptors, probably interacting with the serotonergic transmission, are involved in anxiogenic/prostress processes. In this respect antagonists of the brain mineralocorticoid-like (type I) receptors may be important antistress drugs of the future.