Relationship between dopaminergic neurotransmission, alcoholism, and reward deficiency syndrome

Abdalla Bowirrat, Marlene Oscar-Berman

Research output: Contribution to journalReview articlepeer-review

240 Scopus citations

Abstract

In this review, we described the neural substrates underlying Reward Deficiency syndrome which, in turn, is posited to underlie alcohol dependency. Alcoholism is a complex, multifactorial disorder that results from the interplay between genetic and environmental factors. The D2 dopamine receptor (DRD2) has been associated with pleasure, and the DRD2 A1 allele has been referred to as a reward gene. Evidence suggests that there is a tripartite interaction involving dopamine receptor deficiency, a propensity to abuse alcohol, and reduced sensitivity to rewards. This interaction relies heavily on genetic characteristics of the individual, with certain ethnic groups having a greater tendency toward alcoholism than others. The DRD2 has been one of the most widely studied in neuropsychiatric disorders in general, and in alcoholism and other addictions in particular. The dopamine D2 (DRD2) gene, and especially its allele TaqI A1 allele and its receptor, also may be involved in comorbid antisocial personality disorder symptoms, high novelty seeking, and related traits. The mesocorticolimbic dopaminergic pathway system plays an especially important role in mediating reinforcement by abused drugs, and it may be a common denominator for addictions such as alcoholism. When the mesocorticolimbic dopamine reward system dysfunctions (perhaps caused by certain genetic variants), the end result is Reward Deficiency syndrome and subsequent drug-seeking behaviors. Reward Deficiency syndrome refers to the breakdown of the reward cascade, and resultant aberrant conduct, due to genetic and environmental influences. Alcohol and other drugs of abuse, as well as most positive reinforcers, cause activation and neuronal release of brain dopamine, which can decrease negative feelings and satisfy abnormal cravings. A deficiency or absence of DRD2 receptors then predisposes individuals to a high risk for multiple addictive, impulsive, and compulsive behaviors. Although other neurotransmitters (e.g., glutamate, gamma-aminobutyric acid (GABA), and serotonin) may be important in determining the rewarding and stimulating effects of ethanol, dopamine may be critical for initiating drug use and for reinstating drug use during protracted abstinence.

Original languageEnglish
Pages (from-to)29-37
Number of pages9
JournalAmerican Journal of Medical Genetics, Part B: Neuropsychiatric Genetics
Volume132 B
Issue number1
DOIs
StatePublished - 5 Jan 2005
Externally publishedYes

Keywords

  • Addiction
  • Association
  • D2 dopamine receptor gene
  • Linkage disequilibrium
  • Mesocorticolimbic system
  • Neurotransmitters
  • Reward

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