Neuropeptide Y blocks anxiogenic-like behavioral action of corticotropin-releasing factor in an operant conflict test and elevated plus maze

Central administration of neuropeptide Y (NPY) produces anxiolytic-like beh avioral effects in rat models of anxiety. Because previous evidence has sug gested a relationship between NPY and corticotropin-releasing factor (CRF) in the brain, we have focused on the interaction of these neuropeptide syst ems in emotional responsiveness to stressful stimuli. Intracerebroventricul ar administration of CRF produced a marked response suppression in an opera nt incremental shock conflict paradigm. NPY [(1 mu g, intracerebroventricul arly (i.c.v.)] significantly antagonized the response-suppressing effects o f CRF (0.75 mu g, i.c.v.) on punished responding in the conflict test at do ses that produced little or no behavioral effect when administered alone. C entral administration of the CRF antagonist [D-Phe(12), Nle(21,38),C-alpha MeLeu(37)]CRF (D-Phe CRF12-41) alone did not alter punished or unpunished r esponding in the conflict test. However, pretreatment with the CRF antagoni st before a subthreshold dose of NPY (1 mu g, i.c.v.) produced a significan t potentiation of the release of punished responding relative to NPY alone and untreated controls. NPY also antagonized the "anxiogenic-like" behavior al effects of CRF in the elevated plus maze. These findings support the hyp othesis that NPY and CRF may reciprocally modulate an animal's behavioral r esponse to stressful stimuli. (C) 2000 Elsevier Science Inc. All rights res erved.