Chronic psychosocial stress reduces the density of dopamine transporters.

The effect of different types of physical stress on brain dopaminergic function has been well established in rodents; however, the role of the dopaminergic system in more naturalistic stress situations is poorly understood. Therefore, the aim of the current study was to investigate the effect of chronic psychosocial stress on the dopamine transporter, which is an important component in the regulation of dopaminergic neurotransmission. For this purpose, we used the well-characterized paradigm of subordination stress in male tree shrews (Tupaia belangeri). In the present study, the animals were subjected to psychosocial stress for 28 days. Animals were daily videotaped and locomotor activity was quantified. In subordinate animals, urinary cortisol and noradrenaline, as well as adrenal weight, were increased, whereas body weight, locomotor activity and testicular function were decreased. Brain dopamine transporter binding sites were quantified by in vitro autoradiography using [3H] WIN 35,428 as ligand. Chronic stress reduced the number of binding sites (Bmax) in the caudate nucleus and the putamen without affecting the affinity (Kd). Stress did not influence the binding parameters in the nucleus accumbens, the substantia nigra or the ventral tegmental area. Furthermore, we found a positive correlation between locomotor activity and the Bmax values for [3H] WIN 35,428 binding in the caudate nucleus, the putamen and the nucleus accumbens. The present study shows that a naturalistic stressor, such as chronic psychosocial conflict, decreases dopamine transporter binding sites in motor-related brain areas, suggesting that the reduction in locomotor activity in subordinate tree shrews is related to the downregulation of dopamine transporter binding sites.