Antidepressant effects of thyrotropin-releasing hormone analogues using a rodent model of depression

The antidepressant potential of two naturally occurring analogues of thyrot ropin-releasing hormone (TRH), pGLU-GLU-PRO-NH2 (EEP) and pGLU-PHE-PRO-NH2 (EFP), were examined using a rodent model of antidepressant efficacy. The P orsolt Swim Test was used to assay the antidepressant proper-ties of these two peptides. Both analogues of TRH produced significant antidepressant eff ects, with EEP producing the stronger response. No effect of EEP upon triio dothyronine (T-3) was observed at the dosage used. EFP, which has previousl y been demonstrated to crossreact with the TRH receptor, significantly incr eased serum T-3. Since an effect upon T-3 was only observed in the weaker o f the two compounds, these data suggest that the behavioral effect of EEP w as not secondary to stimulation of thyroid hormone. Additionally, the diffe rential behavioral response to the two compounds suggests a degree of seque nce specificity in the ability of TRH-like tripeptides to produce an antide pressant effect. (C) 2001 Elsevier Science Inc. All rights reserved.