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The effects of Ro 64‐6198 and diazepam on antinociception and remifentanil self‐administration in rhesus monkeys
Author(s) -
Podlesnik Christopher A.,
Ko MeiChuan,
Winger Gail,
Woods James H.
Publication year - 2010
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.24.1_supplement.765.1
Subject(s) - diazepam , chemistry , flumazenil , nop , agonist , pharmacology , antagonist , benzodiazepine , anxiolytic , endocrinology , receptor , medicine , biochemistry
The aim of this study was to compare the behavioral effects of a synthetic nonpeptidic NOP (nociceptin/orphanin FQ Peptide) receptor agonist, Ro 64‐6198, with a benzodiazepine, diazepam, in rhesus monkeys. Ro 64‐6198 (0.001–0.01 mg/kg, i.v.) produced antinociception against an acute noxious stimulus (50 degrees C water), but diazepam (0.32–3.2 mg/kg, i.v.) did not produce such effects at any dose tested. Higher doses of Ro 64‐6198 (0.32 mg/kg, i.v.) and diazepam (1.0–5.6 mg/kg, i.v.) decreased lever pressing maintained by intravenous self‐administration of the mu‐opioid agonist, remifentanil. Although neither drug increased nonreinforced responding with complete consistency, such effects were more frequent with diazepam. These effects of Ro 64‐6198 on lever pressing were blocked by an NOP‐receptor antagonist, J‐113397, but not by the benzodiazepine antagonist, flumazenil. Conversely, the effects of diazepam on lever pressing were blocked by flumazenil but not J‐113397. These findings suggest the effects of Ro 64‐6198 on operant lever pressing are mediated by NOP receptors and that higher doses are required compared to those producing antinociception. Moreover, Ro 64‐6198 was less likely to disinhibit nonreinforced operant responding than diazepam, suggesting diazepam might produce greater anxiolytic‐like effects than Ro 64‐6198 in rhesus monkeys.