Approach to the genetics of alcoholism: A review based on pathophysiology

Köhnke, Michael D.

doi:10.1016/j.bcp.2007.06.021

Cited by 105 publications

(76 citation statements)

References 216 publications

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“…The dopamine receptors can subdivided in two families: D1 family (dopamine D1 receptor (D1R) and D5R) and D2 family (D2R, D3R, and D4R) (Bordet 2004;Le Foll et al 2009;Nieoullon and Amalric 2002;Sibley 1999;Velasco et al 2002;Velasco and Luchsinger 1998;Verheij and Cools 2008). Most importantly, genetic studies have found associations between the dopaminergic system and alcoholism, including the identification of gene polymorphisms for some dopamine receptors (Ball and Murray 1994;Kohnke 2008;Li 2000;Tiihonen et al 1995;Tyndale 2003), but not all reports are in agreement (Bolos et al 1990). Thus, there is a putative genetic and physiological link between dopaminergic neurotransmission and ethanol abuse.…”

Section: Introductionmentioning

confidence: 99%

Involvement of nucleus accumbens dopamine D1 receptors in ethanol drinking, ethanol-induced conditioned place preference, and ethanol-induced psychomotor sensitization in mice

Bahí

Dreyer

2012

Psychopharmacology

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Rationale Dopamine D1 receptor (D1R) signaling has been associated to ethanol consumption and reward in laboratory animals. Objectives Here, we hypothesize that this receptor, which is located within the nucleus accumbens (NAc) neurons, modulates alcohol reward mechanisms. Methods To test this hypothesis, we measured alcohol consumption and ethanol-induced psychomotor sensitization and conditioned place preference (CPP) in mice that received bilateral microinjections of small interference RNA (siRNA)-expressing lentiviral vectors (LV-siD1R) producing D1R knock-down. The other group received control (LV-Mock) viral vectors into the NAc. Results There were no differences in the total fluid consumed and also no differences in the amount of ethanol consumed between groups prior to surgery. However, after surgery, the LV-siD1R group consumed less ethanol than the control group. This difference was not associated to taste neophobia. In addition, results have shown that downregulation of endogenous D1R using viral-mediated siRNA in the NAc significantly decreased ethanol-induced behavioral sensitization as well as acquisition, but not expression, of ethanol-induced place preference.Conclusions We conclude that decreased D1R expression into the NAc led to reduced ethanol rewarding properties, thereby leading to lower voluntary ethanol consumption. Together, these findings demonstrate that the D1 receptor pathway within the NAc controls ethanol reward and intake.

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Section: Introductionmentioning

confidence: 99%

Involvement of nucleus accumbens dopamine D1 receptors in ethanol drinking, ethanol-induced conditioned place preference, and ethanol-induced psychomotor sensitization in mice

Bahí

Dreyer

2012

Psychopharmacology

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“…Accordingly, one should consider alcohol addiction as a heterogeneous disorder considering both the etiology and phenotype 5,6 . Differences in phenotype characteristics are reflected in the age at addiction onset, alcohol disease history and history of drinking, comorbid disorders, and occurrence of abstinence difficulties.…”

Section: Icd-10 = International Statistical Classification Of Diseasementioning

confidence: 99%

“…Results of numerous family studies, twin studies and adoptive studies point to the fact that alcoholism addiction is hereditary in more than 50% of cases 5,7,31 , and, even more, the alcohol intake model itself is hereditary as well (alcohol quantity, frequency of intoxication, etc.) 8,36 .…”

Section: Genetic Basis Of Alcohol Addictionmentioning

confidence: 99%

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Neurobiological Bases of Alcohol Addiction

Matošić¹,

Marušić²,

Vidrih³

et al. 2016

ACC

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SUMMARY -Alcohol addiction is a heterogeneous psychiatric disorder according to both phenotype and etiology. Difference in phenotype characteristics manifests in the manner the addiction arises, history of the alcoholic and history of drinking, comorbid disorders, and the phenomenon of abstinence difficulties. Concerning the etiology of alcoholism, the disease itself is considered to be a consequence of an interactive influence of the environment and genetic factors. Numerous researches conducted in the last decades discovered many aspects of the biochemical, cell and molecular bases of alcohol addiction, leading to a conclusion that alcoholism is, like many other addictions, a brain disease. By recognizing alcoholism as a disease which basically implies changes of the neurobiological mechanisms, as well as a clear genetic basis, it was supposed that the disease, having its basis solely in the symptomatology, is essentially heterogeneous. By trying to solve the problem of a clinically heterogeneous nature of the disease during the last fifty years, various sub-classifications of such patients have been suggested. According to Cloninger, subtypes of alcoholism differ also according to changes in the brain neurotransmission systems, i.e. it is supposed that patients suffering from alcoholism type 1 have a more pronounced dopaminergic transmission deficit, while dopaminergic transmission is not disturbed significantly in patients diagnosed with alcoholism type 2, who, however, have a significant lack of serotonergic transmission. In such a way, Cloninger actually presented the basis of the so-called neurobiological alcoholism model. Since he has connected differences in neurotransmission with differences in personality characteristics, this model is also known as the psychobiological model of alcoholism. The characteristic of alcoholism type 1 is avoiding damage (Harm Avoidance, HA) decreased dopamine transmission and increased serotonin transmission, while the significant characteristic of alcoholism type 2 is seeking for excitement (Novelty Seeking, NS), unchanged dopamine transmission and decreased serotonin transmission. These neurochemical differences among alcoholism subtypes represent the basis for a different therapy approach. Intake of alcohol changes different gene expression in the human brain. The inheritance model of alcoholism is not fully explained, however, it is considered that the disease is connected to a larger gene number included in neurotransmission, cell mechanisms and general metabolic function, with a simultaneous influence of the environment. The contribution of genetic factors is stronger in certain types of alcoholism and thus we have been confronted in the last years of alcoholism research with studies researching the connections of some alcoholism subtypes with the polymorphism phenomenon in the genes coding the synaptic proteins included in the alcoholism etiology. The primary role of monoamine oxidase (MAO) in the brain is catalysis of deamination of the oxidative neurotransmitter a...

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“…This complex disease, precipitated by the interaction between biological, genetic and environmental risk factors, is heterogeneous in its etiology and phenotype characteristics, such as the age of onset, drinking behavior, as well as comorbid disorders (Köhnke, 2008). The findings that alcoholism shows no classic pattern of inheritance, and that alcohol affects various targets in the brain, suggest that genetic vulnerability to alcoholism is likely to be due to multiple contributing genes encoding proteins in many neurotransmitter systems and signal transduction pathways (Enoch, 2008).…”

Section: Introductionmentioning

confidence: 99%