Overlapping neuronal substrates of reactivity to drug, gambling, food and sexual cues: a comprehensive meta-analysis

First published: 30/03/2019 | Last updated: May 20th, 2019


Professor Rainer Spanagel

Journal Editor

Rainer Spanagel studied biology at the Universities of Tübingen and Munich and pursued his early training in behavioural pharmacology and neurochemistry at the Max Planck Institute (MPI) in Martinsried. In 1990, he moved to the MPI of Psychiatry in Munich and became head of the addiction research group and was awarded a lectureship in Pharmacology and Toxicology. In 2000, he relocated to the Central Institute of Mental Health in Mannheim, a leading European institution for biological psychiatry, to become scientific director of the Institute of Psychopharmacology. Professor Spanagel has been awarded many scientific prizes, most notably the Sir Hans Krebs Award for his seminal gene x environment study in rodents, the James B. Isaacson Award he received in 2008 for his continuing achievements in alcohol research, and the Reinhardt Koselleck Award for innovation in neuroscience. He has published more than 250 articles and is Editor-in-Chief of In Silico Pharmacology and Addiction Biology.

Rainer Spanagel, Alejandro Cosa Linan, Hamid R. Noori*,


Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany


Background: Cue reactivity to natural and social rewards is essential for motivational behavior. However, cue reactivity to drug rewards can also elicit craving in addicted subjects. The degree to which drug and natural rewards share neural substrates is not known. The objective of this study is to conduct a comprehensive meta-analysis of neuroimaging studies on drug, gambling and natural stimuli (food and sex) to identify the common and distinct neural substrates of cue reactivity to drug and natural rewards.

Methods: Neural cue reactivity studies were selected for the meta-analysis by means of activation likelihood estimations, followed by sensitivity and clustering analyses of averaged neuronal response patterns.

Findings: Data from 176 studies (5573 individuals) suggests largely overlapping neural response patterns towards all tested reward modalities. Common cue reactivity to natural and drug rewards was expressed by bilateral neural responses within anterior cingulate gyrus, insula, caudate head, inferior frontal gyrus, middle frontal gyrus and cerebellum. However, drug cues also generated distinct activation patterns in medial frontal gyrus, middle temporal gyrus, posterior cingulate gyrus, caudate body and putamen. Natural reward cues induced unique activation of the pulvinar in thalamus; especially for sexual cues.

Interpretation: Neural substrates of cue reactivity to alcohol, drugs of abuse, food, sex and gambling are largely overlapping and comprise a network that processes emotional responses, habit formation and reward. This suggests that cue-mediated craving involves mechanisms that are not exclusive for addictive disorders but rather resemble the intersection of information pathways for processing emotional responses, non-declarative memory and obsessive-compulsive behavior.


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