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Compulsive alcohol seeking and relapse: Central role of conditioning factors associated with alleviation of withdrawal states by alcohol
BACKGROUND AND PURPOSE: Learned associations between environmental stimuli and drugs of abuse represent a major factor in the chronically relapsing nature of drug addiction. In drug dependent subjects these associations must be presumed to include associations linked to reversal of adverse withdrawa...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388476/ https://www.ncbi.nlm.nih.gov/pubmed/35411600 http://dx.doi.org/10.1111/bph.15854 |
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author | Kozanian, Olga O. Nedelescu, Hermina Kufahl, Peter R. Mayford, Mark Weiss, Friedbert |
author_facet | Kozanian, Olga O. Nedelescu, Hermina Kufahl, Peter R. Mayford, Mark Weiss, Friedbert |
author_sort | Kozanian, Olga O. |
collection | PubMed |
description | BACKGROUND AND PURPOSE: Learned associations between environmental stimuli and drugs of abuse represent a major factor in the chronically relapsing nature of drug addiction. In drug dependent subjects these associations must be presumed to include associations linked to reversal of adverse withdrawal states by drug use—“withdrawal‐associated learning” (WDL). However, their significance in drug seeking has received little experimental scrutiny. EXPERIMENTAL APPROACH: Using alcohol as a drug of abuse, the behavioural consequences of WDL were investigated in animal models of relapse and compulsive drug seeking by comparing the effects of WD L‐associated stimuli versus stimuli associated with alcohol without WDL experience in nondependent and post‐dependent rats. Brain sites activated by exposure to the respective stimuli were identified by c‐fos immunohistochemistry. KEY RESULTS: (1) WDL‐associated stimuli elicited significant alcohol seeking. In rats with WDL experience, stimuli associated with alcohol in the nondependent state no longer elicited robust alcohol seeking. (2) Responding elicited by WDL‐associated stimuli, but not stimuli conditioned to alcohol in the nondependent state, was resistant to footshock punishment and increased response effort requirements for presentation of WDL‐related stimuli. (3) Stimuli conditioned to alcohol in rats with a dependence but not WDL history did not sustain punished responding or tolerance of increased effort. (4) The central nucleus of the amygdala was identified as a site selectively responsive to WDL stimulus exposure. CONCLUSION AND IMPLICATIONS: Environmental stimuli associated with reversal of adverse withdrawal states by alcohol elicit compulsive‐like alcohol seeking and establish WDL as a major, not well‐recognized factor, in relapse vulnerability. |
format | Online Article Text |
id | pubmed-9388476 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93884762022-10-14 Compulsive alcohol seeking and relapse: Central role of conditioning factors associated with alleviation of withdrawal states by alcohol Kozanian, Olga O. Nedelescu, Hermina Kufahl, Peter R. Mayford, Mark Weiss, Friedbert Br J Pharmacol Research Articles BACKGROUND AND PURPOSE: Learned associations between environmental stimuli and drugs of abuse represent a major factor in the chronically relapsing nature of drug addiction. In drug dependent subjects these associations must be presumed to include associations linked to reversal of adverse withdrawal states by drug use—“withdrawal‐associated learning” (WDL). However, their significance in drug seeking has received little experimental scrutiny. EXPERIMENTAL APPROACH: Using alcohol as a drug of abuse, the behavioural consequences of WDL were investigated in animal models of relapse and compulsive drug seeking by comparing the effects of WD L‐associated stimuli versus stimuli associated with alcohol without WDL experience in nondependent and post‐dependent rats. Brain sites activated by exposure to the respective stimuli were identified by c‐fos immunohistochemistry. KEY RESULTS: (1) WDL‐associated stimuli elicited significant alcohol seeking. In rats with WDL experience, stimuli associated with alcohol in the nondependent state no longer elicited robust alcohol seeking. (2) Responding elicited by WDL‐associated stimuli, but not stimuli conditioned to alcohol in the nondependent state, was resistant to footshock punishment and increased response effort requirements for presentation of WDL‐related stimuli. (3) Stimuli conditioned to alcohol in rats with a dependence but not WDL history did not sustain punished responding or tolerance of increased effort. (4) The central nucleus of the amygdala was identified as a site selectively responsive to WDL stimulus exposure. CONCLUSION AND IMPLICATIONS: Environmental stimuli associated with reversal of adverse withdrawal states by alcohol elicit compulsive‐like alcohol seeking and establish WDL as a major, not well‐recognized factor, in relapse vulnerability. John Wiley and Sons Inc. 2022-05-01 2022-09 /pmc/articles/PMC9388476/ /pubmed/35411600 http://dx.doi.org/10.1111/bph.15854 Text en © 2022 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Research Articles Kozanian, Olga O. Nedelescu, Hermina Kufahl, Peter R. Mayford, Mark Weiss, Friedbert Compulsive alcohol seeking and relapse: Central role of conditioning factors associated with alleviation of withdrawal states by alcohol |
title | Compulsive alcohol seeking and relapse: Central role of conditioning factors associated with alleviation of withdrawal states by alcohol |
title_full | Compulsive alcohol seeking and relapse: Central role of conditioning factors associated with alleviation of withdrawal states by alcohol |
title_fullStr | Compulsive alcohol seeking and relapse: Central role of conditioning factors associated with alleviation of withdrawal states by alcohol |
title_full_unstemmed | Compulsive alcohol seeking and relapse: Central role of conditioning factors associated with alleviation of withdrawal states by alcohol |
title_short | Compulsive alcohol seeking and relapse: Central role of conditioning factors associated with alleviation of withdrawal states by alcohol |
title_sort | compulsive alcohol seeking and relapse: central role of conditioning factors associated with alleviation of withdrawal states by alcohol |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9388476/ https://www.ncbi.nlm.nih.gov/pubmed/35411600 http://dx.doi.org/10.1111/bph.15854 |
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