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Review
. 2020 Jul 30;12(8):2288.
doi: 10.3390/nu12082288.

Underlying Susceptibility to Eating Disorders and Drug Abuse: Genetic and Pharmacological Aspects of Dopamine D4 Receptors

Luca Botticelli  1 , Emanuela Micioni Di Bonaventura  1 , Fabio Del Bello  2 , Gianfabio Giorgioni  2 , Alessandro Piergentili  2 , Adele Romano  3 , Wilma Quaglia  2 , Carlo Cifani  1 , Maria Vittoria Micioni Di Bonaventura  1
Affiliations
Review

Underlying Susceptibility to Eating Disorders and Drug Abuse: Genetic and Pharmacological Aspects of Dopamine D4 Receptors

Luca Botticelli et al. Nutrients. .

Abstract

The dopamine D4 receptor (DRD4) has a predominant expression in the prefrontal cortex (PFC), brain area strictly involved in the modulation of reward processes related to both food and drug consumption. Additionally, the human DRD4 gene is characterized by a variable number of tandem repeats (VNTR) in the exon 3 and, among the polymorphic variants, the 7-repeat (7R) allele appears as a contributing factor in the neurobiological mechanisms underlying drug abuse, aberrant eating behaviors and related comorbidities. The 7R variant encodes for a receptor with a blunted intracellular response to dopamine, and carriers of this polymorphism might be more tempted to enhance dopamine levels in the brain, through the overconsumption of drugs of abuse or palatable food, considering their reinforcing properties. Moreover, the presence of this polymorphism seems to increase the susceptibility of individuals to engage maladaptive eating patterns in response to negative environmental stimuli. This review is focused on the role of DRD4 and DRD4 genetic polymorphism in these neuropsychiatric disorders in both clinical and preclinical studies. However, further research is needed to better clarify the complex DRD4 role, by using validated preclinical models and novel compounds more selective for DRD4.

Keywords: 7-repeat allele; DRD4 agonist; DRD4 antagonist; dopamine D4 receptor (DRD4); drug addiction; eating behavior; food addiction; obesity; prefrontal cortex; reward.

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Conflict of interest statement

The authors declare no conflict of interest.

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