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The selective κ-opioid receptor antagonist JDTic attenuates the alcohol deprivation effect in rats.
- Source :
-
European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology [Eur Neuropsychopharmacol] 2019 Dec; Vol. 29 (12), pp. 1386-1396. Date of Electronic Publication: 2019 Oct 31. - Publication Year :
- 2019
-
Abstract
- The mechanisms behind relapse to ethanol intake in recovering alcoholics are still unclear. The negative reinforcing effects contributing to ethanol addiction, including relapse, are considered to be partly driven by the κ-opioidergic system. As the κ-opioidergic system interacts with the mesolimbic reward pathway, the aim of the study was to clarify the role of nucleus accumbens shell κ-opioidergic mechanisms in relapse to ethanol intake by using the alcohol deprivation effect (ADE) paradigm. The ADE is defined as a transient increase in voluntary ethanol intake after a forced period of abstinence. Male Long-Evans rats were trained to voluntarily consume 10% (v/v) ethanol solution. Ethanol access and deprivation cycles were initiated after stable ethanol intake baselines had been reached and bilateral guide cannulas had been implanted above the nucleus accumbens shell. One cycle consisted of 10 days of 90 min access to ethanol followed by 6 days of ethanol deprivation. The ADE was measured in the beginning of a new cycle. Rats received JDTic, a selective κ-antagonist, either subcutaneously (10 mg/kg) or intra-accumbally (15 µg/site) or, as a reference substance, systemic naltrexone (0.3 mg/kg) before ethanol re-access, and the effects on the ADE were evaluated. Systemic and intra-accumbal JDTic significantly attenuated the ADE on the first day of ethanol re-access, as did systemic naltrexone. Additionally, naltrexone decreased ethanol intake levels. These results suggest that nucleus accumbens shell κ-opioidergic mechanisms may have a role in mediating relapse to ethanol intake. Additionally, κ-antagonism could be a valuable adjunct in ethanol relapse prevention.<br /> (Copyright © 2019 Elsevier B.V. and ECNP. All rights reserved.)
- Subjects :
- Alcohol Deterrents pharmacology
Alcohol Deterrents therapeutic use
Alcohol Drinking metabolism
Alcohol Drinking psychology
Animals
Ethanol administration & dosage
Male
Naltrexone pharmacology
Naltrexone therapeutic use
Narcotic Antagonists pharmacology
Piperidines pharmacology
Rats
Rats, Long-Evans
Receptors, Opioid, kappa metabolism
Self Administration
Tetrahydroisoquinolines pharmacology
Alcohol Abstinence psychology
Alcohol Drinking prevention & control
Narcotic Antagonists therapeutic use
Piperidines therapeutic use
Receptors, Opioid, kappa antagonists & inhibitors
Tetrahydroisoquinolines therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7862
- Volume :
- 29
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 31679889
- Full Text :
- https://doi.org/10.1016/j.euroneuro.2019.10.003