Blockade of brain dopamine receptors antagonizes the anti-immobility effect of MIF-1 and Tyr-MIF-1 in rats.

Previous studies have shown effects of MIF-1 (prolyl-leucyl-glycinamide) and Tyr-MIF-1 (tyrosyl-prolyl-leucyl-glycinamide) in animal models of depression and also effects on dopaminergic function. These observations prompted us to examine whether the effects of the two peptides in the behavioral 'despair' test were modulated by dopamine antagonists. MIF-1 and Tyr-MIF-1, at the small dose of 0.01 mg/kg i.p. (24, 5 and 1 h before the test), produced a significant anti-immobility effect. This effect was antagonized by a single injection of either haloperidol or sulpiride, two dopamine receptor blockers. The same low dose of the tricyclic antidepressant desipramine was without significant effect in this test. The results indicate that Tyr-MIF-1, like MIF-1, is active in the behavioral despair test for antidepressants and that at least some of the CNS actions of these peptides are mediated by dopamine receptors.