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The novel μ-opioid receptor antagonist GSK1521498 decreases both alcohol seeking and drinking: evidence from a new preclinical model of alcohol seeking
Chiara Giuliano,Charles R. Goodlett,Daina Economidou,María Pilar García-Pardo,David Belin,Trevor W. Robbins,Edward T. Bullmore,Edward T. Bullmore,Barry J. Everitt +8 more
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TLDR
C cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective μ-opioid receptor antagonist, on both voluntary alcohol-intake and alcohol- seeking behaviors and showed significantly greater effectiveness than nALTrexone, supporting its potential use for promoting abstinence and preventing relapse in alcohol addiction.Abstract:
Distinct environmental and conditioned stimuli influencing ethanol-associated appetitive and consummatory behaviors may jointly contribute to alcohol addiction. To develop an effective translational animal model that illuminates this interaction, daily seeking responses, maintained by alcohol-associated conditioned stimuli (CSs), need to be dissociated from alcohol drinking behavior. For this, we established a procedure whereby alcohol seeking maintained by alcohol-associated CSs is followed by a period during which rats have the opportunity to drink alcohol. This cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective μ-opioid receptor antagonist, on both voluntary alcohol-intake and alcohol-seeking behaviors. Rederived alcohol-preferring, alcohol-nonpreferring, and high-alcohol-drinking replicate 1 line of rats (Indiana University) first received 18 sessions of 24 h home cage access to 10% alcohol and water under a 2-bottle choice procedure. They were trained subsequently to respond instrumentally for access to 15% alcohol under a second-order schedule of reinforcement, in which a prolonged period of alcohol-seeking behavior was maintained by contingent presentations of an alcohol-associated CS acting as a conditioned reinforcer. This seeking period was terminated by 20 min of free alcohol drinking access that achieved significant blood alcohol concentrations. The influence of pretreatment with either naltrexone (0.1-1-3 mg/kg) or GSK1521498 (0.1-1-3 mg/kg) before instrumental sessions was measured on both seeking and drinking behaviors, as well as on drinking in the 2-bottle choice procedure. Naltrexone and GSK1521498 dose-dependently reduced both cue-controlled alcohol seeking and alcohol intake in the instrumental context as well as alcohol intake in the choice procedure. However, GSK1521498 showed significantly greater effectiveness than naltrexone, supporting its potential use for promoting abstinence and preventing relapse in alcohol addiction.read more
Citations
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In search of predictive endophenotypes in addiction: insights from preclinical research
TL;DR: The principal findings emanating from preclinical animal research on addiction are surveyed and discussed to highlight how specific behavioral endophenotypes of presumed genetic origin differentially contribute to compulsive forms of drug seeking and taking and, in particular, how these differentiate between different classes of stimulant and non‐stimulant drugs of abuse.
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Improving translation of animal models of addiction and relapse by reverse translation.
TL;DR: A reverse translational approach is proposed, whose goal is to develop models that mimic successful treatments: opioid agonist maintenance, contingency management and the community-reinforcement approach that may provide an ecologically relevant platform from which to discover new circuits, test new medications and improve translation.
Journal ArticleDOI
Understanding Addiction Using Animal Models.
TL;DR: The most common preclinical models of addictive behavior, including non-contingent models in which animals are passively exposed to rewarding substances, as well as widely used contingent models such as drug self-administration and relapse are reviewed.
Journal ArticleDOI
Evidence for a Long-Lasting Compulsive Alcohol Seeking Phenotype in Rats.
Chiara Giuliano,Yolanda Peña-Oliver,Charles R. Goodlett,Rudolf N. Cardinal,Trevor W. Robbins,Edward T. Bullmore,Edward T. Bullmore,David Belin,Barry J. Everitt +8 more
TL;DR: Novel evidence is provided for the existence in rats of an individual vulnerability to switch from controlled to compulsive, punishment-resistant alcohol seeking, and it is shown that a selective and potent μ-opioid receptor antagonist reduced both alcohol seeking and alcohol intake in compulsive and non-compulsive rats, indicating its therapeutic potential to promote abstinence and prevent relapse in individuals addicted to alcohol.
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Addictive behaviour in experimental animals: prospects for translation
TL;DR: The psychological and neural mechanisms underlying drug memory reconsolidation and extinction established in animal experiments show particular promise in delivering new treatments for relapse prevention to the clinic.
References
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