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.
Mishra
R K
RK
Department of Psychiatry, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.
Marcotte
E R
ER
Chugh
A
A
Barlas
C
C
Whan
D
D
Johnson
R L
RL
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology*; D004357:Drug Synergism; D007980:Levodopa / Q000494:pharmacology; D009075:MSH Release-Inhibiting Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects*
D018491:Dopamine Agonists; D011760:Pyrrolidinones; C067487:3-(N-prolylamine)-2-oxo-1-pyrrolidineacetamide; D019257:Quinpirole; D007980:Levodopa; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; D009075:MSH Release-Inhibiting Hormone; D001058:Apomorphine; D004298:Dopamine