Maria E Secci1, Julie A Factor1, Charles W Schindler1, Leigh V Panlilio2. 1. Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, 251 Bayview Blvd, Baltimore, MD, USA. 2. Preclinical Pharmacology Section, Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, US Department of Health and Human Services, 251 Bayview Blvd, Baltimore, MD, USA. lpanlili@intra.nida.nih.gov.
Abstract
RATIONALE: The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. OBJECTIVES: To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 μg/kg) and delayed delivery of palatable food pellets. RESULTS: Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding. CONCLUSIONS: These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction.
RATIONALE: The choice to seek immediate drug effects instead of more meaningful but delayed rewards is a defining feature of addiction. OBJECTIVES: To develop a rodent model of this behavior, we allowed rats to choose between immediate intravenous delivery of the prescription opioid oxycodone (50 μg/kg) and delayed delivery of palatable food pellets. RESULTS:Rats preferred food at delays up to 30 s, but they chose oxycodone and food equally at 60-s delay and preferred oxycodone over food at 120-s delay. Comparison of food-drug choice, food-only, and drug-only conditions indicated that food availability decreased drug intake, but drug availability increased food intake. In the food-only condition, food was effective as a reinforcer even when delayed by 120 s. Pre-session feeding with chow slowed acquisition of food and drug self-administration, but did not affect choice. To establish procedures for testing potential anti-addiction medications, noncontingent pre-treatment with oxycodone or naltrexone (analogous to substitution and antagonist therapies, respectively) were tested on a baseline in which oxycodone was preferred over delayed food. Naltrexone pre-treatment decreased drug intake and increased food intake. Oxycodone pre-treatment decreased drug intake, but also produced extended periods with no food or drug responding. CONCLUSIONS: These findings show that the contingencies that induce preference for drugs over more meaningful but less immediate rewards in humans can be modeled in rodents, and they suggest that the model could be useful for assessing the therapeutic potential of treatments and exploring the underlying behavioral and neural mechanisms involved in addiction.
Authors: Jennifer L Perry; Erin B Larson; Jonathan P German; Gregory J Madden; Marilyn E Carroll Journal: Psychopharmacology (Berl) Date: 2004-08-27 Impact factor: 4.530
Authors: Tommy Gunawan; Yosuke Hachiga; Christopher S Tripoli; Alan Silberberg; David N Kearns Journal: Psychopharmacology (Berl) Date: 2020-01-29 Impact factor: 4.530
Authors: Leigh V Panlilio; Maria E Secci; Charles W Schindler; Charles W Bradberry Journal: Psychopharmacology (Berl) Date: 2017-09-04 Impact factor: 4.530