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-NH, (PLG) peptidomimetic analogue 3(R) [(2(S) pyrrolidinylcarbonyl)amino]-2-oxo 1 pyrrolidineacetamide (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 1 DOPA, PAOPA was 100-fold more potent than PLG, and produced a fourfold greater response than PLG when administered IP. PAOPA also potentiated contralateral rotations induced by SKF-38393 and quinipirole. 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.