Specific and Nonspecific Effects of Naltrexone on Goal-Directed and Habitual Models of Alcohol Seeking and Drinking
Background The opioid‐receptor antagonist naltrexone (NTX) reduces goal‐directed alcohol drinking in rats presumably by blunting alcohol reward. However, different operant conditioning behavior can be produced by different reinforcement schedules, with goal‐directed operant behavior being more sensi...
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Published in | Alcoholism, clinical and experimental research Vol. 37; no. 7; pp. 1100 - 1110 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
England
Blackwell Publishing Ltd
01.07.2013
Wiley Subscription Services, Inc |
Subjects | |
Online Access | Get full text |
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Summary: | Background
The opioid‐receptor antagonist naltrexone (NTX) reduces goal‐directed alcohol drinking in rats presumably by blunting alcohol reward. However, different operant conditioning behavior can be produced by different reinforcement schedules, with goal‐directed operant behavior being more sensitive to changes in reward value than less flexible, habit‐associated models. We tested the hypothesis that NTX more effectively reduces alcohol drinking and seeking in a goal‐directed than in a habit‐associated operant model, and more effectively reduces alcohol versus sucrose self‐administration, consistent with diminished alcohol reward.
Methods
Rats were trained to self‐administer 10% alcohol or 1.5% sucrose in a lever‐press task and then underwent a within‐subject assessment of NTX (0.1 to 1 mg/kg) effects on operant behavior. A fixed‐ratio (FR5) reinforcement schedule was used to model goal‐directed behavior, and a variable‐interval (VI30) schedule was used to model habitual behavior.
Results
As predicted, NTX reduced fluid deliveries earned by the FR5‐alcohol group significantly more than all other groups. However, NTX reduced lever presses during self‐administration sessions in VI30‐trained rats without reducing earned deliveries, due to the low contingency between rate of pressing and fluid deliveries under that schedule. Interestingly, when fluid delivery was withheld (extinction), NTX reduced reward‐seeking in all rats. Finally, NTX blocked reinstatement of reward‐seeking upon presentation of 0.2 ml alcohol or sucrose and associated cues in the FR5‐trained but not VI30‐trained rats.
Conclusions
NTX reduced goal‐directed alcohol drinking compared with other operant conditions. In addition, NTX blocked reinstatement of reward‐seeking in rats trained on the goal‐directed FR5 reinforcement schedule but not in rats trained on the habit‐like VI30 reinforcement schedule. However, NTX also exerted nonspecific effects on reward‐seeking that were revealed under low‐effort contingency conditions or absence of reward. Together, these data support the hypothesis that NTX is less effective in conditioning models that are more habit‐associated. |
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Bibliography: | UNC Bowles Center for Alcohol Studies ark:/67375/WNG-034KRNG8-C ArticleID:ACER12081 Foundation of Hope Table S1. Naltrexone Effects on Reward-Seeking During Brief Extinction SessionsTable S2. Behavior, Ethanol Dose and Blood Ethanol Concentration (BEC) from Rats Self-Administering 10% Ethanol on FR5 and VI30 Reinforcement Schedules UNC Office of Undergraduate Research istex:9D51ED6B710C35C3C2BA577520A8FD6931E55EF5 NIH - No. AA018008 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Equal contribution to manuscript |
ISSN: | 0145-6008 1530-0277 |
DOI: | 10.1111/acer.12081 |