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The nociceptin/orph...
The nociceptin/orphanin FQ receptor agonist SR-8993 as a candidate therapeutic for alcohol use disorders: validation in rat models
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- Aziz, Abdul Maruf Asif (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Brothers, Shaun (author)
- University of Miami Health System, University of Miami, Miami, USA
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- Sartor, Gregory (author)
- University of Miami Health System, University of Miami, Miami, USA
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- Holm, Lovisa (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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- Heilig, Markus (author)
- Linköpings universitet,Avdelningen för neuro- och inflammationsvetenskap,Medicinska fakulteten,Centrum för social och affektiv neurovetenskap (CSAN),Region Östergötland, Psykiatriska kliniken
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- Wahlestedt, Claes (author)
- University of Miami Health System, University of Miami, Miami, USA
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- Thorsell, Annika (author)
- Linköpings universitet,Avdelningen för cellbiologi,Medicinska fakulteten
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(creator_code:org_t)
- 2016-08-11
- 2016
- English.
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In: Psychopharmacology. - : Springer. - 0033-3158 .- 1432-2072. ; 233:19-20, s. 3553-3563
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https://link.springe...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- RATIONALE: Alcoholism is a complex disorder in which diverse pathophysiological processes contribute to initiation and progression, resulting in a high degree of heterogeneity among patients. Few pharmacotherapies are presently available, and patient responses to these are variable. The nociceptin/orphanin FQ (NOP) receptor has been suggested to play a role both in alcohol reward and in negatively reinforced alcohol seeking. Previous studies have shown that NOP-receptor activation reduces alcohol intake in genetically selected alcohol-preferring as well as alcohol-dependent rats. NOP activation also blocks stress- and cue-induced reinstatement of alcohol-seeking behavior.OBJECTIVES: Here, we aimed to examine a novel, potent, and brain-penetrant small-molecule NOP-receptor agonist, SR-8993, in animal models of alcohol- as well as anxiety-related behavior using male Wistar rats.RESULTS: SR-8993 was mildly anxiolytic when given to naïve animals and potently reversed acute alcohol withdrawal-induced ("hangover") anxiety. SR-8993 reduced both home-cage limited access drinking, operant responding for alcohol, and escalation induced through prolonged intermittent access to alcohol. SR-8993 further attenuated stress- as well as cue-induced relapse to alcohol seeking. For the effective dose (1.0 mg/kg), non-specific effects such as sedation may be limited, since a range of control behaviors were unaffected, and this dose did not interact with alcohol elimination.CONCLUSION: These findings provide further support for NOP-receptor agonism as a promising candidate treatment for alcoholism and establish SR-8993 or related molecules as suitable for further development as therapeutics.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Hälsovetenskap -- Beroendelära (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Health Sciences -- Substance Abuse (hsv//eng)
Keyword
- Nociception/orphanin FQ
- Agonist
- Wistar rat
- Alcohol
- Operant
- Reinstatement
- Elevated plus-maze
Publication and Content Type
- ref (subject category)
- art (subject category)
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