Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female rats

Operant self-administration is frequently used to investigate the neurobiological mechanisms underlying alcohol seeking and drinking and to evaluate treatments of alcohol use disorder (AUD). Although widely used by the research community, there is a paucity of operant ethanol self-administration stu...

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Main Authors: Joseph R Pitock, Shannon R Wheeler, Arleen Perez Ayala, Shikun Hou, Nathaly M Arce Soto, Elizabeth J Glover
Format: Article
Language:English
Published: Elsevier 2025-06-01
Series:Addiction Neuroscience
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772392525000045
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author Joseph R Pitock
Shannon R Wheeler
Arleen Perez Ayala
Shikun Hou
Nathaly M Arce Soto
Elizabeth J Glover
author_facet Joseph R Pitock
Shannon R Wheeler
Arleen Perez Ayala
Shikun Hou
Nathaly M Arce Soto
Elizabeth J Glover
author_sort Joseph R Pitock
collection DOAJ
description Operant self-administration is frequently used to investigate the neurobiological mechanisms underlying alcohol seeking and drinking and to evaluate treatments of alcohol use disorder (AUD). Although widely used by the research community, there is a paucity of operant ethanol self-administration studies that include female subjects. The current study characterizes home cage drinking and operant ethanol self-administration in female Sprague Dawley, Long Evans, and Wistar rats. Rats underwent three weeks of intermittent-access two-bottle choice home cage drinking before being trained to lever press for ethanol in standard operant chambers equipped with contact lickometers. After capturing baseline operant performance, rats were chronically exposed to control or ethanol liquid diet using the Lieber-DeCarli method followed by re-evaluation of operant performance during acute withdrawal. Our findings reveal the presence of three distinct operant phenotypes, the prevalence of which within each strain is strikingly similar to our previous observations in males. Within a given phenotype, rats of each strain performed similarly during operant testing. Ethanol intake during home cage drinking was unable to predict future operant phenotype. Relative to controls, Drinkers chronically exposed to ethanol liquid diet exhibited a significant, but transient, escalation in consummatory, but not appetitive, responding during acute withdrawal. Collectively, these data closely parallel many of our previous observations in males while also highlighting potential sex differences in drinking strategies following dependence. Our findings provide new insight into similarities and differences in operant ethanol self-administration between males and females and emphasize the importance of including females in future studies of ethanol drinking and dependence.
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spelling doaj-art-2b0acf6e860f4420851461bc6383a1b72025-02-06T05:13:03ZengElsevierAddiction Neuroscience2772-39252025-06-0115100198Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female ratsJoseph R Pitock0Shannon R Wheeler1Arleen Perez Ayala2Shikun Hou3Nathaly M Arce Soto4Elizabeth J Glover5Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USACenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USACenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USACenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USACenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USACorrespondence author at: Center for Alcohol Research in Epigenetics Department of Psychiatry University of Illinois at Chicago 1601 W Taylor St, MC912, Rm 418 Chicago, IL.; Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USAOperant self-administration is frequently used to investigate the neurobiological mechanisms underlying alcohol seeking and drinking and to evaluate treatments of alcohol use disorder (AUD). Although widely used by the research community, there is a paucity of operant ethanol self-administration studies that include female subjects. The current study characterizes home cage drinking and operant ethanol self-administration in female Sprague Dawley, Long Evans, and Wistar rats. Rats underwent three weeks of intermittent-access two-bottle choice home cage drinking before being trained to lever press for ethanol in standard operant chambers equipped with contact lickometers. After capturing baseline operant performance, rats were chronically exposed to control or ethanol liquid diet using the Lieber-DeCarli method followed by re-evaluation of operant performance during acute withdrawal. Our findings reveal the presence of three distinct operant phenotypes, the prevalence of which within each strain is strikingly similar to our previous observations in males. Within a given phenotype, rats of each strain performed similarly during operant testing. Ethanol intake during home cage drinking was unable to predict future operant phenotype. Relative to controls, Drinkers chronically exposed to ethanol liquid diet exhibited a significant, but transient, escalation in consummatory, but not appetitive, responding during acute withdrawal. Collectively, these data closely parallel many of our previous observations in males while also highlighting potential sex differences in drinking strategies following dependence. Our findings provide new insight into similarities and differences in operant ethanol self-administration between males and females and emphasize the importance of including females in future studies of ethanol drinking and dependence.http://www.sciencedirect.com/science/article/pii/S2772392525000045DrinkingAlcohol use disorderSex differencesLickometer
spellingShingle Joseph R Pitock
Shannon R Wheeler
Arleen Perez Ayala
Shikun Hou
Nathaly M Arce Soto
Elizabeth J Glover
Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female rats
Addiction Neuroscience
Drinking
Alcohol use disorder
Sex differences
Lickometer
title Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female rats
title_full Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female rats
title_fullStr Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female rats
title_full_unstemmed Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female rats
title_short Presence of distinct operant phenotypes and transient withdrawal-induced escalation of operant ethanol intake in female rats
title_sort presence of distinct operant phenotypes and transient withdrawal induced escalation of operant ethanol intake in female rats
topic Drinking
Alcohol use disorder
Sex differences
Lickometer
url http://www.sciencedirect.com/science/article/pii/S2772392525000045
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