Anxiolytic activity of NPY receptor agonists in the conflict test

Anxiolytic activity of NPY receptor agonists in the conflict test This investigation examined receptor subtype specificity and possible modulation by GABAa receptor ligands of NPY-induced behavioral responses to stressful stimuli. First, a series of NPY receptor agonists were examined for their potential effects on punished responding in a conflict test modified for incremental shock. NPY, peptide YY (PYY) and NPY Y 1 receptor agonists (Leu 31 ,Pro 34 )-NPY and (Gly 6 , Glu 26 ,Lys 29 ,Pro 34 )-NPY produced increases in punished responding in the conflict test. No significant effects on unpunished responding were noted. The pattern of responding was similar to that observed with the benzodiazepine agonist chlordiazepoxide. Neither pancreatic peptide (PP) nor the Y 2 agonists NPY 13–36 or (Glu 2,32 ,Ala 6 ,Dpr 27 ,Lys 28 )-NPY significantly altered punished or unpunished responding. Of significance, the atypical Y 1 agonist (Cys 7,21 ,Pro 34 )-NPY produced negligible effects on punished responding, consistent with the presence of a subclass of Y 1 receptors. Second, the anxiolytic effects of NPY were subjected to treatments that block actions at the GABAa receptor complex. The increase in punished responding produced by NPY was not altered by administration of the benzodiazepine antagonist flumazenil and only partially blocked by the picrotoxinin receptor ligand isopropylbicyclophosphate (10 and 15 μg/kg). These findings further support the hypothesis that the pharmacologic substrates for the anxiolytic-like actions of NPY may be mediated by the Y 1 receptor subtype and suggest that these actions are independent of either the benzodiazepine or picrotoxinin binding sites of the GABA/benzodiazepine receptor complex. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Psychopharmacology Springer Journals

Anxiolytic activity of NPY receptor agonists in the conflict test

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Publisher
Springer Journals
Copyright
Copyright © 1997 by Springer-Verlag Berlin Heidelberg
Subject
Legacy
ISSN
0033-3158
eISSN
1432-2072
DOI
10.1007/s002130050313
Publisher site
See Article on Publisher Site

Abstract

This investigation examined receptor subtype specificity and possible modulation by GABAa receptor ligands of NPY-induced behavioral responses to stressful stimuli. First, a series of NPY receptor agonists were examined for their potential effects on punished responding in a conflict test modified for incremental shock. NPY, peptide YY (PYY) and NPY Y 1 receptor agonists (Leu 31 ,Pro 34 )-NPY and (Gly 6 , Glu 26 ,Lys 29 ,Pro 34 )-NPY produced increases in punished responding in the conflict test. No significant effects on unpunished responding were noted. The pattern of responding was similar to that observed with the benzodiazepine agonist chlordiazepoxide. Neither pancreatic peptide (PP) nor the Y 2 agonists NPY 13–36 or (Glu 2,32 ,Ala 6 ,Dpr 27 ,Lys 28 )-NPY significantly altered punished or unpunished responding. Of significance, the atypical Y 1 agonist (Cys 7,21 ,Pro 34 )-NPY produced negligible effects on punished responding, consistent with the presence of a subclass of Y 1 receptors. Second, the anxiolytic effects of NPY were subjected to treatments that block actions at the GABAa receptor complex. The increase in punished responding produced by NPY was not altered by administration of the benzodiazepine antagonist flumazenil and only partially blocked by the picrotoxinin receptor ligand isopropylbicyclophosphate (10 and 15 μg/kg). These findings further support the hypothesis that the pharmacologic substrates for the anxiolytic-like actions of NPY may be mediated by the Y 1 receptor subtype and suggest that these actions are independent of either the benzodiazepine or picrotoxinin binding sites of the GABA/benzodiazepine receptor complex.

Journal

PsychopharmacologySpringer Journals

Published: Jul 1, 1997

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