Converging vulnerability factors for compulsive food and drug use

Serafine, Katherine M.; O’Dell, Laura E.; Zorrilla, Eric P.

doi:10.1016/j.neuropharm.2021.108556

Cited by 13 publications

(11 citation statements)

References 663 publications

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“…Data on the influence of DA genes polymorphisms on the psychopathological features displayed by patients with EDs are still lacking, especially in comparison with the abundance of the paper published on serotonergic polymorphisms. Emerging evidence suggest that the neural mechanisms implicated in the appetitive motivation for drugs and those involved in appetitive motivation for the food show the same core features ( 69 , 70 ). This supports the “food addiction” hypothesis according to which, both drugs of abuse and food consumption activate the same brain pathway where the dopaminergic signaling is the principal neurotransmission system involved in reward and motivation ( 27 , 69 ).…”

Section: Discussionmentioning

confidence: 99%

Association Between DRD2 and DRD4 Polymorphisms and Eating Disorders in an Italian Population

et al. 2022

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Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are the three most common eating disorders (EDs). Their etiopathogenesis is multifactorial where both the environmental and genetic factors contribute to the disease outcome and severity. Several polymorphisms in genes involved in the dopaminergic pathways seem to be relevant in the susceptibility to EDs, but their role has not been fully elucidated yet. In this study, we have analyzed the association between selected common polymorphisms in the DRD2 and DRD4 genes in a large cohort of Italian patients affected by AN (n = 332), BN (n = 122), and BED (n = 132) compared to healthy controls (CTRs) (n = 172). Allelic and genotypic frequencies have been also correlated with the main psychopathological and clinical comorbidities often observed in patients. Our results showed significant associations of the DRD2-rs6277 single nucleotide polymorphism (SNP) with AN and BN, of the DRD4-rs936461 SNP with BN and BED and of DRD4 120-bp tandem repeat (TR) polymorphism (SS plus LS genotypes) with BED susceptibility. Moreover, genotyping of DRD4 48-bp variable number TR (VNTR) identified the presence of ≥7R alleles as risk factors to develop each type of EDs. The study also showed that ED subjects with a history of drugs abuse were characterized by a significantly higher frequency of the DRD4 rs1800955 TT genotype and DRD4 120-bp TR short-allele. Our findings suggest that specific combinations of variants in the DRD2 and DRD4 genes are predisposing factors not only for EDs but also for some psychopathological features often coupled specifically to AN, BN, and BED. Further functional research studies are needed to better clarify the complex role of these proteins and to develop novel therapeutic compounds based on dopamine modulation.

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Section: Discussionmentioning

confidence: 99%

Association Between DRD2 and DRD4 Polymorphisms and Eating Disorders in an Italian Population

et al. 2022

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“…We used rats in the current study, because rats are known to replicate aspects of neurobehavioural profiles of human drug addiction and disordered eating (Serafine et al, 2021; Volkow & Wise, 2005). For all cases, studies were designed to generate groups of equal size, using randomization and blinded analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Similarly, extensive obesogenic diet histories can cause addiction‐like food motivation and brain changes in animals (Wiss et al, 2017). Because patients with drug addiction—as a universally recognized form of addiction—and people with obesity and/or eating disorders—as putative ‘food addiction’—share similar brain profiles (Serafine et al, 2021; Volkow & Wise, 2005), we hypothesized that extensive drug histories would similarly cause punishment‐resistant operant food self‐administration or ‘compulsive appetite’ in animals.…”

Section: Introductionmentioning

confidence: 99%

Linking drug and food addiction via compulsive appetite

Laque

Wagner

Matzeu

et al. 2022

British J Pharmacology

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Background and Purpose ‘Food addiction’ is the subject of intense public and research interest. However, this nosology based on neurobehavioural similarities among obese individuals, patients with eating disorders and those with substance use disorders (drug addiction) remains controversial. We thus sought to determine which aspects of disordered eating are causally linked to preclinical models of drug addiction. We hypothesized that extensive drug histories, known to cause addiction‐like brain changes and drug motivation in rats, would also cause addiction‐like food motivation. Experimental Approach Rats underwent extensive cocaine, alcohol, caffeine or obesogenic diet histories and were subsequently tested for punishment‐resistant food self‐administration or ‘compulsive appetite’, as a measure of addiction‐like food motivation. Key Results Extensive cocaine and alcohol (but not caffeine) histories caused compulsive appetite that persisted long after the last drug exposure. Extensive obesogenic diet histories also caused compulsive appetite, although neither cocaine nor alcohol histories caused excess calorie intake and bodyweight during abstinence. Hence, compulsive appetite and obesity appear to be dissociable, with the former sharing common mechanisms with preclinical drug addiction models. Conclusion and Implications Compulsive appetite, as seen in subsets of obese individuals and patients with binge‐eating disorder and bulimia nervosa (eating disorders that do not necessarily result in obesity), appears to epitomize ‘food addiction’. Because different drug and obesogenic diet histories caused compulsive appetite, overlapping dysregulations in the reward circuits, which control drug and food motivation independently of energy homeostasis, may offer common therapeutic targets for treating addictive behaviours across drug addiction, eating disorders and obesity.

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“…While genetic linkage and association approaches such as Genome-Wide Association Studies (GWAS) have been widely used to identify candidate genes in humans (Hall et al, 2013(Hall et al, , 2020Serafine et al, 2021), to date few genes identified by GWAS have been verified by clinical or preclinical studies. Another major approach used to identify specific risk genes has been the examination of candidate genes that encode proteins that are critically involved in the pharmacological action of misused drugs, such as genes related to brain dopaminergic, GABAergic, opioid, and cholinergic systems (Hall et al, 2013;Serafine et al, 2021). Transgenic approaches have been valuable in identifying genes and proteins relevant to SUD, such as µ opioid receptors (MOR) for opioid action, dopamine transporters (DAT) for cocaine action, and the vesicular monoamine transporter 2 (VMAT2) for amphetamine and methamphetamine action (Sora et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…While genetic linkage and association approaches such as Genome-Wide Association Studies (GWAS) have been widely used to identify candidate genes in humans ( Hall et al, 2013 , 2020 ; Serafine et al, 2021 ), to date few genes identified by GWAS have been verified by clinical or preclinical studies. Another major approach used to identify specific risk genes has been the examination of candidate genes that encode proteins that are critically involved in the pharmacological action of misused drugs, such as genes related to brain dopaminergic, GABAergic, opioid, and cholinergic systems ( Hall et al, 2013 ; Serafine et al, 2021 ). Transgenic approaches have been valuable in identifying genes and proteins relevant to SUD, such as μ opioid receptors (MOR) for opioid action, dopamine transporters (DAT) for cocaine action, and the vesicular monoamine transporter 2 (VMAT2) for amphetamine and methamphetamine action ( Sora et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of the Risk Genes Associated With Vulnerability to Addiction: Major Findings From Transgenic Animals

Jordan

2022

Front. Neurosci.

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Understanding risk factors for substance use disorders (SUD) can facilitate medication development for SUD treatment. While a rich literature exists discussing environmental factors that influence SUD, fewer articles have focused on genetic factors that convey vulnerability to drug use. Methods to identify SUD risk genes include Genome-Wide Association Studies (GWAS) and transgenic approaches. GWAS have identified hundreds of gene variants or single nucleotide polymorphisms (SNPs). However, few genes identified by GWAS have been verified by clinical or preclinical studies. In contrast, significant progress has been made in transgenic approaches to identify risk genes for SUD. In this article, we review recent progress in identifying candidate genes contributing to drug use and addiction using transgenic approaches. A central hypothesis is if a particular gene variant (e.g., resulting in reduction or deletion of a protein) is associated with increases in drug self-administration or relapse to drug seeking, this gene variant may be considered a risk factor for drug use and addiction. Accordingly, we identified several candidate genes such as those that encode dopamine D2 and D3 receptors, mGluR2, M4 muscarinic acetylcholine receptors, and α5 nicotinic acetylcholine receptors, which appear to meet the risk-gene criteria when their expression is decreased. Here, we describe the role of these receptors in drug reward and addiction, and then summarize major findings from the gene-knockout mice or rats in animal models of addiction. Lastly, we briefly discuss future research directions in identifying addiction-related risk genes and in risk gene-based medication development for the treatment of addiction.

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Converging vulnerability factors for compulsive food and drug use

Cited by 13 publications

References 663 publications

Association Between DRD2 and DRD4 Polymorphisms and Eating Disorders in an Italian Population

Association Between DRD2 and DRD4 Polymorphisms and Eating Disorders in an Italian Population

Linking drug and food addiction via compulsive appetite

Identification of the Risk Genes Associated With Vulnerability to Addiction: Major Findings From Transgenic Animals

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