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Preclinical evaluat...
Preclinical evaluation of the kappa-opioid receptor antagonist CERC-501 as a candidate therapeutic for alcohol use disorders
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- Domi, Esi (författare)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Barbier, Estelle (författare)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Augier, Eric (författare)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Augier, Gaëlle (författare)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Gehlert, D. (författare)
- Cerecor, MD USA; Matrix Pharmaceut Consulting, CO USA
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- Barchiesi, Riccardo (författare)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Thorsell, Annika (författare)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Holm, Lovisa (författare)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten
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- Heilig, Markus (författare)
- Linköpings universitet,Centrum för social och affektiv neurovetenskap,Medicinska fakulteten,Region Östergötland, Psykiatriska kliniken
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(creator_code:org_t)
- 2018-02-05
- 2018
- Engelska.
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Ingår i: Neuropsychopharmacology. - : NATURE PUBLISHING GROUP. - 0893-133X .- 1740-634X. ; 43:9, s. 1805-1812
- Relaterad länk:
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https://www.nature.c...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Prior work suggests a role of kappa-opioid signaling in the control of alcohol drinking, in particular when drinking is escalated due to alcohol-induced long-term neuroadaptations. Here, we examined the small molecule selective kappa antagonist CERC-501 in rat models of alcohol-related behaviors, with the objective to evaluate its potential as a candidate therapeutic for alcohol use disorders. We first tested the effect of CERC-501 on acute alcohol withdrawal-induced anxiety-like behavior. CERC-501 was then tested on basal as well as escalated alcohol self-administration induced by 20% alcohol intermittent access. Finally, we determined the effects of CERC-501 on relapse to alcohol seeking triggered by both stress and alcohol-associated cues. Control experiments were performed to confirm the specificity of CERC-501 effects on alcohol-related behaviors. CERC-501 reversed anxiety-like behavior induced by alcohol withdrawal. It did not affect basal alcohol self-administration but did dose-dependently suppress self-administration that had escalated following long-term intermittent access to alcohol. CERC-501 blocked relapse to alcohol seeking induced by stress, but not when relapse-like behavior was triggered by alcohol-associated cues. The effects of CERC-501 were observed in the absence of sedative side effects and were not due to effects on alcohol metabolism. Thus, in a broad battery of preclinical alcohol models, CERC-501 has an activity profile characteristic of anti-stress compounds. Combined with its demonstrated preclinical and clinical safety profile, these data support clinical development of CERC-501 for alcohol use disorders, in particular for patients with negatively reinforced, stress-driven alcohol seeking and use.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Neurovetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Neurosciences (hsv//eng)
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