3 years ago

Cerebral dopaminergic and glutamatergic transmission relate to different subjective responses of acute alcohol intake: an in vivo multimodal imaging study

Cerebral dopaminergic and glutamatergic transmission relate to different subjective responses of acute alcohol intake: an in vivo multimodal imaging study
Cleo Lina Crunelle, Guy Bormans, Jenny Ceccarini, Koen Van Laere, Bart Laat, Akila Weerasekera, Gil Leurquin-Sterk, Uwe Himmelreich
Converging preclinical evidence links extrastriatal dopamine release and glutamatergic transmission via the metabotropic glutamate receptor 5 (mGluR5) to the rewarding properties of alcohol. To date, human evidence is lacking on how and where in the brain these processes occur. Mesocorticolimbic dopamine release upon intravenous alcohol administration and mGluR5 availability were measured in 11 moderate social drinkers by single-session [18F]fallypride and [18F]FPEB positron emission tomography, respectively. Additionally, baseline and postalcohol glutamate and glutamine levels in the anterior cingulate cortex (ACC) were measured by using proton-magnetic resonance spectroscopy. To investigate differences in reward domains linked to both neurotransmitters, regional imaging data were related to subjective alcohol responses. Alcohol induced significant [18F]fallypride displacement in the prefrontal cortex (PFC), temporal and parietal cortices and thalamus (P < 0.05, corrected for multiple comparisons). Dopamine release in the ACC and orbitofrontal and ventromedial PFCs were correlated with subjective ‘liking’ and ‘wanting’ effects (P < 0.05). In contrast, baseline mGluR5 availability was positively correlated with the ‘high’ effect of alcohol in dorsolateral, ventrolateral and ventromedial PFCs and in the medial temporal lobe, thalamus and caudate nucleus (P < 0.05). Although neither proton-magnetic resonance spectroscopy glutamate nor glutamine levels were affected by alcohol, baseline ACC glutamate levels were negatively associated with the alcohol ‘liking’ effect (P < 0.003). These data reveal new mechanistic understanding and differential neurobiological underpinnings of the effects of acute alcohol consumption on human behavior. Specifically, prefrontal dopamine release may encode alcohol ‘liking’ and ‘wanting’ effects in specific areas underlying value processing and motivation, whereas mGluR5 availability in distinct prefrontal–temporal–subcortical regions is more related to the alcohol ‘high’ effect. In this multimodal imaging study, we linked estrastriatal dopamine (DA) release and glutamatergic transmission to the rewarding properties of alcohol in social drinkers. Overall, our human data revealed new mechanistic understanding and differential neurobiological underpinnings of the effects of acute alcohol consumption on human behavior. Specifically, prefrontal DA release may encode alcohol ‘liking’ and ‘wanting’ effects in specific areas underlying value processing and motivation, whereas mGluR5 availability in distinct prefrontal–temporal–subcortical regions is more related to the alcohol ‘high’ effect.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/adb.12542

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