The polymorphism of dopamine D2 receptor TaqIA gene is associated with brain response to drug cues in male heroin-dependent individuals during methadone maintenance treatment.

ABSTRACT

BACKGROUND: Polymorphism of the dopamine D2 receptor TaqIA gene is related to reward response, relapse risks and effect of therapy for drug addiction. Whether the cue-induced craving and brain response was related to dopamine D2 receptor TaqIA gene is unknown. METHODS: Forty-nine male heroin-dependent individuals [31 with A1 allele of the TaqIA (A1+), 18 A2 allele carriers (A1-)] under methadone maintenance treatment and 20 healthy control subjects performed a heroin cue-reactivity task during functional magnetic resonance imaging. Cue-elicited craving was measured. Difference in cue induced craving and brain response were analyzed among the three groups. Correlation analyses between craving and differential brain response, heroin use and treatment history were performed within A1+ and A1- group respectively. RESULTS: Compared with A1- group, A1+ group showed greater cue-induced response in the ventrolateral prefrontal cortex, medial orbitofrontal gyrus, dorsomedial prefrontal cortex, pallidum, putamen, thalamus, superior parietal lobule and superior occipital gyrus. No difference in craving was found. The response in right thalamus positively correlated with daily heroin and methadone dose in A1+ group. For A1- group, response in left ventral orbitofrontal cortex, medial orbitofrontal gyrus, ventral anterior cingulate cortex, caudate, precuneus, calcarine and bilateral pallidum negatively correlated with duration of heroin use. The response in left ventral orbitofrontal cortex, medial orbitofrontal gyrus, bilateral calcarine and right cerebellum negatively correlated with duration of methadone maintenance treatment in A1- group. CONCLUSIONS: The findings supported that A1 allele of the TaqIA is associated with higher salience allocation to heroin-related cues in heroin-dependent patients.