The alpha-2B adrenoceptor in the paraventricular thalamic nucleus is persistently upregulated by chronic psychosocial stress

Abstract

Stress has been reported to regulate adrenergic receptors but it is not known whether it has an impact on the alpha-2 adrenoceptor subtype B that is strongly expressed in distinct nuclei of the thalamus. So far little is known about effects of stress on the thalamus. Using the chronic psychosocial stress paradigm in male tree shrews, we analyzed alpha-2B adrenoceptor expression in the paraventricular and the anteroventral nucleus of the thalamus after a six-week period of daily social stress and after a 10-day post-stress recovery period. In situ hybridization with a specific alpha-2B adrenoceptor probe was performed to quantify receptor gene expression in single neurons, and receptor binding was determined by in vitro receptor autoradiography using the radioligand [3H]RX821002. To determine the stress level in the animals, we measured urinary cortisol excretion and body weight. In the neurons of the paraventricular thalamic nucleus, expression of the alpha-2B adrenoceptor transcript was increased after both the six-week chronic-stress period and the post-stress recovery period. Combination of in situ hybridization and immunocytochemistry revealed expression of alpha-2B adrenoceptor transcript in neurons that were stained with an antibody against glutamate but not in neurons immunoreactive for GABA. Alpha-2 adrenoceptor radioligand binding was also increased after both time periods in the paraventricular thalamic nucleus. No significant effects of stress and recovery were observed in the anteroventral thalamic nucleus. Urinary cortisol excretion was increased during the stress period but normalized thereafter. Body weight was reduced during weeks 1 to 3 of stress and then normalized. These data show that long-term chronic psychosocial stress has an impact on alpha-2B adrenoceptor expression in the thalamus and that the effect persists throughout a post-stress recovery period though activity of the hypothalamic pituitary adrenal axis normalizes after stress. Upregulation of the receptor probably alters neurotransmission in the paraventricular thalamic nucleus and may thus influence information transfer to limbic and cortical brain areas.