Effects of immobilization stress on neurochemical markers in the motivational system of the male rat.

Mesolimbic regions involved in motivated behavior are altered in animals undergoing repeated exposure to social stress. Here we test the hypothesis that other forms of persistent stress would also influence these same endpoints. Adult male Sprague-Dawley rats were exposed to immobilization stress either once (2 h) or repeatedly (2 hx10 days) and brains were harvested immediately after the last immobilization. A trio of indirect markers associated with dopaminergic activity was measured including dopamine transporter (DAT) and dopamine D2 receptor subtype (D2r) ligand levels as well as mRNA levels of the endogenous opioid enkephalin (ENK-mRNA). A single 2-h session of immobilization stress produced an increase in striatal ENK-mRNA levels and DAT ligand binding compared with group-housed controls. In animals undergoing repeated immobilization stress and singly housed post-stress, we found a significant reversal in the direction of ENK-mRNA levels and DAT binding in the striatum, in addition to an increase in D2r-binding density in the shell of the nucleus accumbens compared with single-stress-exposed rats. In another experiment using the same stress paradigm but allowing pair-housing post-stress, we found no alteration of ENK-mRNA but significant increases in DAT and D2r binding in the dorsal striatum. A major difference between single and group housing is the habituation of the corticosterone (CORT) stress response over 10-day stress in group-housed rats. The present results parallel previous findings by our laboratory that repeated stress results in a relative reduction of ENK-mRNA levels and increased D2r-binding density in the striatum of rats. Furthermore, our data are consistent with the hypothesis that chronic stress induces an allostatic attenuation of the mesolimbic dopaminergic system in animals that do not habituate to the stressor, possibly due in part to persistent CORT elevations.