Stress and the brain: Solving the puzzle using microdialysis

Aberrant functioning of the hypothalamic–pituitary–adrenocortical (HPA) axis seems to be involved in depression and anxiety. However, the mechanisms underlying the relationship between stress and mental illness are not completely resolved yet. The therapeutical efficacy of selective serotonin re-uptake inhibitors and benzodiazepines points to a key role of serotonin and gamma-aminobutyric acid (GABA) in depression and anxiety. Thus, it can be hypothesised that stress-induced changes in serotonin and GABA contribute to a dysregulation of the HPA axis and to the development of psychiatric disorders in susceptible subjects. It will, therefore, be crucial to increase our understanding of the effects of stress on serotonin and GABA. Various refinements have made in vivo microdialysis an extremely powerful method to study the highly dynamic neurotransmitter responses in stress physiology and behaviour. Furthermore, microdialysis can also be used to measure free corticosterone levels in the brain and, thus, HPA axis activity and neurotransmission can be monitored concomitantly. Here we review the effects of acute and chronic stress on serotonin and GABA, as assessed by microdialysis, in the hippocampus; a brain structure critically involved in the behavioural and neuroendocrine responses to stress. From the microdialysis data discussed, it can be concluded that both serotonin and GABA in the hippocampus are highly responsive to stress, but also that these responses are shaped by the exact nature of the stressor, i.e. the balance between the psychological and physical aspects of the stressful challenge.