Changes in dopamine receptor mRNA expression following chronic mild stress and chronic antidepressant treatment

This study used in-situ hybridization to examine D-1 and D-2 receptor mRNA expression in the brains of rats subjected to chronic mild stress and/or chronic treatment (5 weeks) with the antidepressant drugs imipramine and fluoxetine. As in previous studies using the chronic mild stress procedure, stress decreased the consumption of a palatable sucrose solution, and both antidepressants reversed this effect. In-situ hybridization to D-1 and D-2 receptor probes was studied in midbrain and forebrain sections. In the midbrain sections, stress decreased the D-2 receptor message in the substantia nigra and in the lateral part of the ventral tegmental area (VTA), but not in the medial part of the VTA. Imipramine, but not fluoxetine, increased the D-2 receptor message in the VTA, but only in the non-stressed group. In the basal ganglia, stress decreased the D-2 receptor message in the nucleus accumbens (core and shell) and in the lateral, but not the medial, part of the caudate nucleus, in both control and stressed groups. Both imipramine and fluoxetine increased the D-2 receptor message in the lateral, but not the medial, part of the caudate nucleus and in the shell, but not the core, of the nucleus accumbens. There were no significant changes in D-1 receptor message. The results, which are consistent in some respects, and inconsistent in others, with predictions from earlier work, support the hypothesis that forebrain dopamine systems are involved in mediating the behavioural effects of chronic mild stress and their reversal by antidepressants.