Antidepressant Effects of TRH Analogue EEP in Female and Male Rats Assessed with the Forced Swim Test and BDNF Assay

Abstract

The endogenous peptide pGLU-GLU-PRO-NH2 (EEP) has antidepressant effects in male rats demonstrated by decreased immobility in the forced swim test (FST). EEP is a chemical analog of thyrotropin-releasing hormone (TRH), which has short-term antidepressant effects by intrathecal administration in humans. In people with depression, brain-derived neurotrophic factor (BDNF) is decreased in the hippocampus and frontal cortex which leads to decreased volume in both. When people are successfully treated for depression, irrespective of the treatment type, BDNF and volume increase in the hippocampus and frontal cortex, which can indicate recovery. Sex differences are present in the occurrence and symptoms of depression; however, female animals are not always represented in depression research. Female sex hormones are thought to be a reason for sex differences related to depression, and BDNF is known to fluctuate over the estrous cycle of female rats. This study sought to determine if the antidepressant effects of EEP are related to BDNF levels in rats. This study found no significant effects with the forced swim test (FST) and immobility but had a large effect size. A minor sex difference was present in the FST (p = 0.03). Rats that received EEP were not found to have significantly increased levels of BDNF in the hippocampus and frontal cortex, but the results had a large effect size with the frontal cortex. No sex difference was found with BDNF concentrations. Results related to the estrous cycle were insignificant and considered exploratory. The results suggest that continued testing of EEP is needed to gain a greater understanding.