Stress: a major variable in the psychopharmacologic response.

The role of central monoaminergic neurones in stress is undisputed, albeit undefined. This is partly because little is known about the influence of the type or intensity of stress, or subjects' stress history, on monoaminergic transmission. That the presynaptic response is stimulus specific is underlined by a study using in vivo microdialysis in freely moving rats. This indicated that graded changes in noradrenaline efflux in the frontal cortex are produced by progressively increasing the number of novel features in the rats' environment. The influence of receptor status on behavioural responses to stress also depends on the stress imposed. This was suggested by studies showing that rats' behavioural response to stress correlated with the density of cortical beta-adrenoceptors. But the precise relationship again depended on features of the stress, possibly its intensity. Finally, it seems that even a single stress challenge (a 6-min swim) causes a long-latency increase in the density of 5-HT2A receptors in mouse cortex. This upregulation was prevented by a history of intraperitoneal injections of saline but not by injections of the monoamine reuptake blocker sibutramine hydrochloride. Collectively, these experiments emphasize the importance of stress as an experimental variable when studying the actions of psychotropic drugs.