5HT1A-receptors and behaviour under chronic stress: selective counteraction by testosterone.

Behaviour of chronically stressed male tree shrews is characterized by a reduction in scent marking, self-grooming and overall locomotor activity. It has been proposed that this subordination behaviour is related to the down-regulation of 5HT1A-receptors occurring in distinct brain regions of the animals. The high cortisol concentrations which accompany chronic stress are supposed to induce 5HT1A-receptor down-regulation. Because chronic stress in males also decreases androgen levels we investigated whether behaviour and 5HT1A-receptor expression could be renormalized by testosterone replacement. Male tree shrews were submitted to subordination stress for 28 days, while during the last 18 days, one group was treated with testosterone and one with vehicle. Scent marking, self-grooming, and overall locomotor activity were monitored, and cortisol levels were measured in morning urine during the whole experiment. Brain 5HT1A-receptors were quantified by in vitro receptor autoradiography. Although in subordinate animals cortisol levels remained high during the testosterone treatment, 5HT1A-receptors in the hippocampal formation and the occipital cortex were renormalized to control levels by the androgen, but 5HT1A-receptors in the ventromedial thalamic nucleus did not return to base line levels. Scent marking and self-grooming behaviour were both renormalized by testosterone, but overall locomotor activity did not return to base line levels. These data indicate that a balance between glucocorticoids and androgens is necessary to maintain 'normal' numbers of the monoamine receptors. The fact that both, 5HT1A-receptors and certain behaviours can be renormalized by the sex steroid supports the view that 5HT1A-receptor are involved in the regulation of stress behaviour. However, the fact that overall locomotor activity was not returned to baseline indicates that different types of behaviour are distinctly regulated.