title: Low-dose Nociceptin/Orphanin FQ reduces anxiety-like performance in alcohol-withdrawn, but not alcohol-naïve, Male Wistar rats.
abstract: Alcohol withdrawal is associated with neuroadaptation of stress-regulatory systems, including transmission of neuropeptides that have been implicated in anxiety-like performance. Nociceptin/Orphanin FQ (N/OFQ), an endogenous neuropeptide ligand at the NOP receptor, has been implicated in stress and has previously been shown to attenuate or exacerbate anxiety-like performance in rats following a biphasic dose response function. In addition, divergent actions on anxiety-like performance have been observed in alcohol-withdrawn vs. control animals, suggesting alcohol-induced alteration of N/OFQ transmission. In order to differentiate between whether this divergence resulted from a "switch" in the actions of N/OFQ vs. increased sensitivity in N/OFQ transmission, we assessed the actions of low doses of N/OFQ (0, 0.125, 0.25, or 0.5 μg) on two tests of anxiety, the shock-probe defensive burying and elevated plus maze tests, three weeks after the termination of a six-day regimen of alcohol or vehicle administration via intragastric intubation. Consistent with increased sensitivity in N/OFQ resulting from a history of alcohol intake, administration of a low dose of N/OFQ (0.25 μg) selectively attenuated anxiety-like behaviors in animals with a history of alcohol intake while controls did not exhibit any changes in performance. The present results suggest that withdrawal from alcohol produces an enduring increase in sensitivity in N/OFQ transmission - a finding that is consistent with previous studies demonstrating altered transmission in related neuropeptide systems.
authors.affiliation: Department of Psychology, University of Winnipeg, 515 Portage Ave, R3B 2E9 Winnipeg, Canada. Electronic address: h.aujla@uwinnipeg.ca.
authors.forename: Harinder
authors.initials: H
authors.lastname: Aujla
authors.affiliation: Department of Psychology, University of Winnipeg, 515 Portage Ave, R3B 2E9 Winnipeg, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Nedjadrasul
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology*; D002492:Central Nervous System Depressants / Q000633:toxicity; D003674:Defense Mechanisms; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D000431:Ethanol / Q000633:toxicity; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018847:Opioid Peptides / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000150:complications* / Q000209:etiology; D000097629:Nociceptin
chemical_list: D014151:Anti-Anxiety Agents; D002492:Central Nervous System Depressants; D000431:Ethanol; D018847:Opioid Peptides; D000097629:Nociceptin
keywords: Alcohol; Anxiety; Behavior; N/OFQ; Neuropeptides; Stress