Recovery of decreased metabotropic glutamate receptor 5 availability in abstinent alcohol-dependent patients

Abstract

Animal models of alcohol dependence and relapse demonstrate an important role of the glutamatergic system, in particular the cerebral metabotropic glutamate receptor 5 (mGluR5). Using [¹⁸F]FPEB positron emission tomography, it was found that chronic alcohol use leads to decreased limbic mGluR5 availability, where lower mGluR5 was associated with less craving. Here, we tested whether the state of decreased mGluR5 availability in alcohol-dependent patients normalizes during abstinence (at 2- and 6-month of detoxification) and whether initial mGluR5 imaging parameters can predict individual relapse. Methods: [¹⁸F]FPEB scans were performed in 16 recently detoxified alcohol-dependent patients (baseline condition), after 2 months (n = 10) and 6 months (n = 8) of detoxification, in comparison to 32 age- and gender-matched controls. mGluR5 availability was quantified by [¹⁸F]FPEB total distribution volume using both voxel-by-voxel and volume-of-interest analysis. During follow-up, craving was assessed using the Desire for Alcohol Questionnaire, and alcohol consumption was assessed by a Time-Line Follow Back and monitored by hair ethyl glucuronide analysis. Results: During abstinence, alcohol-dependent patients showed a sustained recovered mGluR5 availability in cortical and subcortical regions (p_height<0.001) compared to baseline, up to the levels observed in controls after 6 months in most areas except for the hippocampus, nucleus accumbens and thalamus. A higher striato-pallidal mGlu5 availability was observed at baseline in patients who relapsed during the 6-month follow-up period (+25.1%). Also, normalization of striatal mGlu5 to control levels was associated with reduced craving (“Desire and intention to drink” and “Negative reinforcement”, range r = 0.72-0.94). Conclusion: Reduced cerebral mGluR5 availability in alcohol-dependent patients recovers during abstinence, and is associated with reduced craving. Higher striatal mGluR5 availability in alcohol-dependent users may be associated with long-term relapse.