It is Never as Good the Second Time Around: Brain Areas Involved in Salience Processing Habituate During Repeated Drug Cue Exposure in Methamphetamine and Opioid Users

Abstract

IntroductionThe brain response to drug-related cues is an important marker in addiction-medicine, however, the temporal dynamics of this response in repeated exposure to the cues are not well known yet. In an fMRI drug cue-reactivity task, the presence of rapid habituation or sensitization was investigated by modeling time and its interaction with condition (drug>neutral) using an initial discovery-sample. Replication of this temporal response was tested in two other clinical populations. MethodsSixty-five male participants (35.8{+/-}8.4 years-old) with methamphetamine use disorder (MUD) were recruited as the discovery-sample. A linear mixed effects model was used to identify areas with a time-by-condition interaction in the discovery-sample. Replication of these effects was tested in two other samples (29 female with MUD and 22 male with opioid use disorder). The second replication-sample was re-tested within two weeks. ResultsIn the discovery-sample, clusters within the VMPFC, amygdala and ventral striatum showed both significant condition and condition-by-time interaction with a habituation response for the drug-related cues but not neutral cues. The estimates for the main effects and interactions were generally consistent between the discovery and replication-samples across all clusters. The re-test data showed consistent lack of drug>neutral and habituation response within all selected clusters in the second cue-exposure session. ConclusionsVMPFC, amygdala and ventral striatum show a habituation in response to drug-related cues which is consistent among different clinical populations. Habituation in response in the first session of cue-exposure and lack of reactivity in the second session of exposure provide foundations for development of cue-desensitization interventions.