Modulation of Dopamine Receptor Agonist-Induced Rotational Behavior in 6-OHDA-Lesioned Rats by a Peptidomimetic Analogue of Pro-Leu-Gly-NH2 (PLG)

The present study was undertaken to determine if the previously reported in vitro interactions of the Pro-Leu-Gly-NH2 (PLG) peptidomimetic analogue 3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-2-oxo-1-pyrrolidineacet amide (PAOPA) with the dopaminergic system could be exhibited in an in vivo animal model using 6-hydroxydopamine (6-OHDA)-lesioned rats. In this model, PAOPA was found to potentiate the contralateral rotational behavior induced by either apomorphine or L-DOPA. PAOPA was 100-fold more potent than PLG, and produced a fourfold greater response than PLG when administered i.p. PAOPA also potentiated contralateral rotations induced by SKF-38393 and quinpirole. In summary, the results of this study indicate that PAOPA, a conformationally constrained peptidomimetic analogue of PLG, can modulate dopaminergic activity in vivo with higher potency and efficacy than PLG.