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A novel nociceptin‐1 receptor antagonist produces antidepressant‐ and anxiolytic‐related effects in rodents (656.3)
Author(s) -
Witkin Jeffrey,
Statnick Michael,
RorickKehn Linda,
Barth Vanessa,
Wafford Keith,
Pintar John,
Perry Kenneth,
Toledo Miguel,
Diaz Nuria,
Lafuente Celia,
Jiménez Alma,
Benito Ana,
MartínezGrau Maria Angeles,
Pedregal Conception
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.656.3
Subject(s) - nop , nociceptin receptor , pharmacology , antidepressant , anxiolytic , behavioural despair test , tail suspension test , antagonist , endocrinology , receptor antagonist , medicine , neurochemical , mianserin , chemistry , receptor , serotonin , opioid , hippocampus , opioid peptide
We utilized a potent, selective, and orally‐bio‐available antagonist with documented engagement with nociceptin receptors (NOP) to assess antidepressant‐ and anxioltyic‐related effects of blockade of NOP receptors. The NOP receptor antagonist, Cpd 1, displayed antidepressant‐like neurochemical and behavioral effects in rats and mice. Serotonin outflow in rat prefrontal cortex was enhanced without affecting norepinephrine or dopamine. Correspondingly Cpd 1 decreased immobility in the forced swim test (FST). Cpd 1 augmented the effects of fluoxetine without changing target occupancies of either drug. Anti‐immobility effects of Cpd 1 were absent in mice without NOP receptors. Cpd 1 also produced anxiolytic‐like effects in some rodent models: decreased stimulus‐elicited freezing in mice and decreased stress‐induced hyperthermia in rats. Cdp 1 was not active in: marble‐burying in mice, novelty‐suppressed feeding in mice, conditioned suppression in rats, punished food‐maintained responding in rats, and the 4‐plate test in mice. Cpd 1 did not disrupte performance in 5‐choice serial reaction time tests or delayed matching‐to‐position in rats. Cpd 1 was mildly wake promoting in rats. These data suggest that Cpd 1 has unique antidepressant‐ and anxiolytic‐related pharmacological effects in rodents.