Genes and addiction

  title={Genes and addiction},
  author={Eric J. Nestler},
  journal={Nature Genetics},
  • E. Nestler
  • Published 1 November 2000
  • Psychology, Biology
  • Nature Genetics
Drug addiction, like all psychiatric disorders, is defined solely in behavioural terms. For example, addiction can be considered a loss of control over drug-taking, or compulsive drug-seeking and -taking despite horrendous consequences. Abnormal behaviours are a consequence of aberrant brain function, which means that it is a tangible goal to identify the biological underpinnings of addiction. The genetic basis of addiction encompasses two broad areas of enquiry. One of these is the… 

Learning about addiction from the genome

A draft sequence of the human genome is searched for genes related to desensitization of receptors that mediate the actions of drugs of abuse on the nervous system by searching for genes that contribute to individual risk for addiction.

Experimental Genetic Approaches to Addiction

Understanding Addiction Using Animal Models

The most common preclinical models of addictive behavior, including non-contingent models in which animals are passively exposed to rewarding substances, as well as widely used contingent models such as drug self-administration and relapse are reviewed.

Addictions , genomic findings

This review describes recent findings of addictive drugs-inducing altered changes in gene regulation which produce significant cellular modifications on neuronal function in both human and animal brains as detected in animal models of drug abuse.

Neuroimaging Human Drug Addiction

This chapter explores the addiction syndrome by examining its emotional and cognitive behavioral components with a particular focus on reward valuation and inhibitory control and the brain regions and circuits that subserve them.

Genes associated with addiction

A few selected genetic variants that currently look promising for the study of alcohol, opiate, and cocaine addiction are discussed in this article.

Addiction, neuroscience and ethics.

The challenge is to develop theories of addiction that take seriously the neurobiological bases for drug effects and addictive phenomena without depicting addicts as automatons whose behaviour is under the control of the drugs acting on the receptors sites in their brains.

Molecular basis of long-term plasticity underlying addiction

  • E. Nestler
  • Biology, Psychology
    Nature Reviews Neuroscience
  • 2001
There has been considerable progress in identifying the mechanisms that contribute to long-lived neural and behavioural plasticity related to addiction, including drug-induced changes in gene transcription, in RNA and protein processing, and in synaptic structure.

Genetic contributions to addiction.

  • J. Crabbe
  • Biology, Psychology
    Annual review of psychology
  • 2002
This review selects drug dependence as a paradigmatic addiction, and concentrates on the extensive literature with genetic animal models, both traditional studies with inbred strains and selected lines and studies exploiting the new molecularly based technologies of the genomics era are discussed.



Molecular and cellular basis of addiction.

Current research needs to understand the types of adaptations that underlie the particularly long-lived aspects of addiction, such as drug craving and relapse, and to identify specific genes that contribute to individual differences in vulnerability to addiction.

Molecular mechanisms of drug addiction: adaptations in signal transduction pathways.

The goal of this review is to illustrate how rapidly evolving knowledge of neuronal regulatory mechanisms can be used as a template within which to delineate more complete models of the molecular mechanisms of psychotropic drug action, as well as the role of genetic and environmental factors in determining individual differences in drug responsiveness.

Role for GDNF in Biochemical and Behavioral Adaptations to Drugs of Abuse

Absence of opiate rewarding effects in mice lacking dopamine D2 receptors

The D2 receptor plays a crucial role in the motivational component of drug addiction, as mice lacking D2 receptors behaved the same as wild-type mice when food is used as reward.

Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor

It is proposed that even drug-naive 5-HT1B-knockout mice are in a behavioural and biochemical state that resembles that of wild-type mice sensitized to cocaine by repeated exposure to the drug, which might be responsible for their increased vulnerability to cocaine.

Loss of morphine-induced analgesia, reward effect and withdrawal symptoms in mice lacking the µ-opioid-receptor gene

Investigation of the behavioural effects of morphine reveals that a lack of μ receptors abolishes the analgesic effect of morphine, as well as place-preference activity and physical dependence, and concludes that the µ-opioid-receptor gene product is a mandatory component of the opioid system for morphine action.

Drug-activation of brain reward pathways.

  • R. Wise
  • Biology, Psychology
    Drug and alcohol dependence
  • 1998

Unresponsiveness to cannabinoids and reduced addictive effects of opiates in CB1 receptor knockout mice.

Observations suggest that the CB1 receptor is involved in the motivational properties of opiates and in the development of physical dependence and extend the concept of an interconnected role of CB1 and opiate receptors in the brain areas mediating addictive behavior.