Chronic mild stress induces widespread decreases in thyroid hormone α1 receptor mRNA levels in brain-Reversal by imipramine

While considerable clinical evidence implicates thyroid hormones (THs) in depressive illness, the specific nature of this involvement remains unclear. The alpha(1) subtype (TR-alpha(1)) is the most abundant TH receptor in brain. Here we investigated changes in TR-alpha(1) mRNA in the chronic mild stress (CMS) model of depression. Rats were exposed to a CMS schedule for 3 weeks, which resulted in a progressive decreases in sucrose preference (an index of anhedonia). They were then treated daily with either imipramine (IMI, 10 mg/kg) or vehicle (VEH) for 2 weeks before being sacrificed for quantitative in situ hybridization analyses of TR-alpha(1) mRNA throughout the brain. Results indicated that CMS followed by VEH induced widespread decreases in TR-alpha(1) mRNA in brain. In contrast, CMS-exposed rats receiving IMI for the last 2 weeks prior to sacrifice showed full recovery of sucrose preference. Furthermore, brain TR-alpha(1) mRNA levels in these animals were similar to those of non-stressed controls receiving either SAL or IMI. These results reveal that TR-alpha(1) mRNA brain levels are very sensitive to CMS effects. The reversal of both anhedonic and TR-alpha(1) effects of CMS by IMI suggests that TR-alpha(1) may play a role both in stress-induced depressive symptoms and in their reversal by antidepressant interventions. (C) 2008 Elsevier Ltd. All rights reserved.