PubMed · 11555907
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
A Oishi, J Kira. 2001. [Myoglobinuria].. https://pubmed.ncbi.nlm.nih.gov/11555907/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
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 D(2) dopamine receptor (DRD(2)) has been associated with pleasure, and the DRD(2) 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 DRD(2) 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 DRD(2) 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. This article contains supplementary material, which may be viewed at the American Journal of Medical Genetics website at http://www.interscience.wiley.com/jpages/0148-7299:1/suppmat/index.html.
Several lines of evidence indicate an involvement of the dopaminergic system in alcoholism, withdrawal, suicidality, and attention-deficit hyperactivity disorder (ADHD). The functionally relevant -141C Ins/Del polymorphism located upstream to exon 1 in the 5'-region of the dopamine D2 receptor (DRD2) gene might be an interesting candidate gene. We investigated a sample of 1,126 well-characterized, primary chronic alcoholics of German descent according to a phenotype-genotype strategy, i.e., alcoholics suffering from severe withdrawal complications such as seizure or delirium, family history positive (FH+) alcoholics, alcoholics with an antisocial personality disorder (ASPD), alcoholics with an ADHD, and type 1 or type 2 alcoholics according to Cloninger's typology. Compared to the control subjects, there was a significant excess of the -141C Del allele in alcoholics with a paternal and grandpaternal history of alcoholism and in alcoholic subgroups with suicidality or without a history of withdrawal symptoms. There were no significant differences in allele frequency between the entire group or subgroups of alcoholics and healthy controls. Therefore, the -141C Del variant of the DRD2 might be a protective factor against the development of withdrawal symptoms. However, it might also be a risk factor in a highly burdened subgroup of alcoholics with a paternal and grandpaternal history of alcoholism and it might contribute to the substantially higher likelihood of suicide in alcoholics.
Explore the source record for details and available documents.