Association of the OPRM1 A118G polymorphism and Pavlovian-to-instrumental transfer: Clinical relevance for alcohol dependence

Background: Pavlovian-to-instrumental transfer (PIT) quantifies the extent to which a stimulus that has been associated with reward or punishment alters operant behaviour. In alcohol dependence (AD), the PIT effect serves as a paradigmatic model of cue-induced relapse. Preclinical studies have suggested a critical role of the opioid system in modulating Pavlovian-instrumental interactions. The A118G polymorphism of the OPRM1 gene affects opioid receptor availability and function. Furthermore, this polymorphism interacts with cue-induced approach behaviour and is a potential biomarker for pharmacological treatment response in AD. In this study, we tested whether the OPRM1 polymorphism is associated with the PIT effect and relapse in AD. Methods: Using a PIT task, we examined three independent samples: young healthy subjects (N = 161), detoxified alcohol-dependent patients (N = 186) and age-matched healthy controls (N = 105). We used data from a larger study designed to assess the role of learning mechanisms in the development and maintenance of AD. Subjects were genotyped for the A118G (rs1799971) polymorphism of the OPRM1 gene. Relapse was assessed after three months. Results: In all three samples, participants with the minor OPRM1 G-Allele (G+ carriers) showed increased expression of the PIT effect in the absence of learning differences. Relapse was not associated with the OPRM1 polymorphism. Instead, G+ carriers displaying increased PIT effects were particularly prone to relapse. Conclusion: These results support a role for the opioid system in incentive salience motivation. Furthermore, they inform a mechanistic model of aberrant salience processing and are in line with the pharmacological potential of opioid receptor targets in the treatment of AD.

Automated summary

The presence of the OPRM1 G-allele was associated with increased expression of the Pavlovian-to-instrumental transfer (PIT) effect and greater susceptibility to relapse in both alcohol-dependent patients and healthy controls. However, relapse in alcohol-dependent patients was not directly linked to the OPRM1 polymorphism, highlighting the importance of the opioid system in incentive salience motivation and the potential pharmacological implications for the treatment of alcohol dependence.