Neural response to alcohol taste cues in youth: effects of the OPRM1 gene.
Genetic variations in the mu-opioid receptor (OPRM1) gene have been related to high sensitivity to rewarding effects of alcohol. The current study focuses on the neural circuitry underlying this phenomenon using an alcohol versus water taste-cue reactivity paradigm in a young sample at relatively early stages of alcohol use, thus limiting the confound of variations in duration of alcohol use. Drinkers (17-21 years old) were selected on genotype carrying the AA-(n = 20) or the AG-(n = 16) variant of the A118G single nucleotide polymorphism (SNP) of the OPRM1 gene (rs1799971), and underwent functional magnetic resonance imaging (fMRI). Magnitude of the neural activity and frontostriatal functional connectivity in response to alcohol versus water were investigated. The AG-group demonstrated reduced activation in prefrontal and parietal regions, including the inferior and middle frontal gyrus, superior and inferior parietal lobule, compared with the AA-group. No activation differences were observed in the mesolimbic pathway. Connectivity from the ventral-striatum to frontal regions for alcohol > water trials was higher in the AG than the AA group. For the dorsal-striatum seed region, the AG group showed increased connectivity to non-PFC regions. These results indicate that adolescents carrying the G-allele may be more vulnerable for the alcohol to hijack the reward system in the absence of frontal control to regulate craving. This implies that findings of hyperactivation in the mesolimbic structures of G-allele carriers in earlier studies might result from both genetic susceptibility and heavy drinking.
Addiction, Development and Psychopathology (ADAPT)-lab, Department of Psychology, University of Amsterdam, The Netherlands.|Department of Psychological Sciences, University of Missouri, Columbia, MO, USA.
Ozlem
O
Korucuoglu
Addiction, Development and Psychopathology (ADAPT)-lab, Department of Psychology, University of Amsterdam, The Netherlands.|Research Centre - Military Mental Health, Ministry of Defense, The Netherlands.
Thomas E
TE
Gladwin
Department of Genome Analysis, Academic Medical Centre, The Netherlands.
Frank
F
Baas
Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
Roel J T
RJT
Mocking
Program for Mood Disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.|University of Groningen, University Medical Center Groningen, Mood and Anxiety Disorders, Department of Psychiatry, The Netherlands.
Henricus G
HG
Ruhé
Department of Radiology, Academic Medical Center, The Netherlands.
Paul F C
PFC
Groot
Addiction, Development and Psychopathology (ADAPT)-lab, Department of Psychology, University of Amsterdam, The Netherlands.
Reinout W
RW
Wiers
D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D001931:Brain Mapping / Q000379:methods; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003463:Cues; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D017450:Receptors, Opioid, mu / Q000235:genetics*; D013649:Taste / Q000502:physiology*; D000066608:Underage Drinking; D055815:Young Adult
D002492:Central Nervous System Depressants; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D000431:Ethanol
Alcohol dependence; OPRM1; cue-reactivity; dorsal/ventral striatum; functional connectivity; imaging genetics