[Mechanism of the antidepressive and learning-stimulating effects of thyroliberin and its analogs]

To define the role of different fragments of TRF molecule in its neurotropic activity a number of newly synthesized dipeptides of pyroglutamic acid with beta-alanine residue, GABA or GABA ester have been studied. The compounds were compared with TRF in their ability to influence spontaneous or amphetamine-stimulated locomotor activity in mice and to affect the elaboration of passive avoidance reflex in rats. Unlike TRF, the pyroglutamate dipeptides studied were shown to exhibit no activity in amphetamine potentiation test, thus providing additional evidence of the importance ofthe "histidylproline" fragment in TRF antidepressant effect. On the other hand, the above pyroglutamate derivatives caused a pronounced improvement in the learning abilities of under-trained rats. These dipeptides were shown to be more active in this test than TRF. This suggests the important role of pyroglutamyl moiety in the stimulation of the learning processes.