MODULATION OF DOPAMINE-RECEPTOR AGONIST-INDUCED ROTATIONAL BEHAVIOR IN 6-OHDA-LESIONED RATS BY A PEPTIDOMIMETIC ANALOG OF PRO-LEU-GLY-NH2 (PLG)

The present study was undertaken to determine if the previously report ed in vitro interactions of the Pro-Leu-Gly-NH2 (PLG) peptidomimetic a nalogue idinylcarbonyl)amino]-2-oxo-1-pyrrolidineacetamide (PAOPA) wit h the dopaminergic system could be exhibited in an in vivo animal mode l 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 administer ed IF. PAOPA also potentiated contralateral rotations induced by SKF-3 8393 and quinpirole. In summary, the results of this study indicate th at PAOPA, a conformationally constrained peptidomimetic analogue of PL G, can modulate dopaminergic activity in vivo with higher potency and efficacy than PLG. (C) 1997 Elsevier Science Inc.