A medium throughput rodent model of relapse from addiction with behavioral and pharmacological specificity

William J.A. Eiler, Scott D. Gleason, Jodi Smith, Jeffrey M. Witkin

Research output: Contribution to journalArticle

Abstract

One of most formidable problems in the treatment of addiction is the high rate of relapse. The discovery of medicines to help mitigate relapse are aided by animal models that currently involve weeks of training and require surgical preparations and drug delivery devices. The present set of experiments was initiated to investigate a rapid 8-day screening method that utilizes food instead of intravenous drug administration. Male Sprague-Dawley rats were trained in a reinstatement paradigm in which every lever press produced a 45 mg food pellet concurrently paired with a light and tone. Behavior was subsequently extinguished with lever responses producing neither food nor food-associated stimuli. Reinstatement of responding was evaluated under conditions in which the first three responses of every 5 min time bin produced a food pellet along with food-associated stimuli. The mGlu5 receptor antagonists MPEP and MTEP produced a significant reduction in reinstatement while failing to alter responding where every response produced food. The cannabinoid CB1 receptor antagonist rimonabant and the mGlu2/3 receptor agonist LY379268 also selectively reduced reinstatement. Other compounds including clozapine, d-amphetamine, chlordiazepoxide, ABT-431, naltrexone and citalopram were without effect. The results suggest that relapse-like behavioral effects can be extended to non-pharmacological reinforcers. Drug effects demonstrated both behavioral and pharmacological specificity. The present experimental design thus allows for efficient and rapid assessment of the effects of drugs that might be useful in the treatment of addiction-associated relapse.

Original languageEnglish (US)
Pages (from-to)72-79
Number of pages8
JournalPharmacology Biochemistry and Behavior
Volume183
DOIs
StatePublished - Aug 1 2019
Externally publishedYes

Fingerprint

Rodentia
Throughput
Pharmacology
Recurrence
Food
rimonabant
LY 379268
Pharmaceutical Preparations
Cannabinoid Receptor Antagonists
Chlordiazepoxide
Cannabinoid Receptor CB1
Citalopram
Dextroamphetamine
Drug Compounding
Naltrexone
Clozapine
Bins
Drug delivery
Intravenous Administration
Design of experiments

ASJC Scopus subject areas

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Clinical Biochemistry
  • Biological Psychiatry
  • Behavioral Neuroscience

Cite this

A medium throughput rodent model of relapse from addiction with behavioral and pharmacological specificity. / Eiler, William J.A.; Gleason, Scott D.; Smith, Jodi; Witkin, Jeffrey M.

In: Pharmacology Biochemistry and Behavior, Vol. 183, 01.08.2019, p. 72-79.

Research output: Contribution to journalArticle

Eiler, William J.A. ; Gleason, Scott D. ; Smith, Jodi ; Witkin, Jeffrey M. / A medium throughput rodent model of relapse from addiction with behavioral and pharmacological specificity. In: Pharmacology Biochemistry and Behavior. 2019 ; Vol. 183. pp. 72-79.
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