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

The antidepressant potential of two naturally occurring analogues of thyrotropin-releasing hormone (TRH), pGLU-GLU-PRO-NH2 (EEP) and pGLU-PHE-PRO-NH2 (EFP), were examined using a rodent model of antidepressant efficacy. The Porsolt Swim Test was used to assay the antidepressant properties of these two peptides. Both analogues of TRH produced significant antidepressant effects, with EEP producing the stronger response. No effect of EEP upon triiodothyronine (T3) was observed at the dosage used. EFP, which has previously been demonstrated to crossreact with the TRH receptor, significantly increased serum T3. Since an effect upon T3 was only observed in the weaker of the two compounds, these data suggest that the behavioral effect of EEP was not secondary to stimulation of thyroid hormone. Additionally, the differential behavioral response to the two compounds suggests a degree of sequence specificity in the ability of TRH-like tripeptides to produce an antidepressant effect.