High ethanol tolerance in young adults is associated with the low-activity variant of the promoter of the human serotonin transporter gene

Türker, Timucin; Sodmann, Richard; Goebel, Ursula; Jatzke, Susanne; Knapp, Michael; Lesch, Klaus‐Peter; Schuster, Rilana; Schütz, H.; Weiler, G; Stöber, Gerald

doi:10.1016/s0304-3940(98)00347-4

Cited by 77 publications

(49 citation statements)

References 13 publications

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“…A large number of reports related genetic and functional alterations in the 5-HTT with the occurrence of depressionand anxiety-related disorders associated to alcohol dependence (Heinz et al, 1998(Heinz et al, , 2000Turker et al, 1998;Mantere et al, 2002;Oroszi and Goldman, 2004). Indeed, the manipulation of the 5-HTT by treatment with selective serotonin reuptake inhibitors (SSRI) has resulted beneficial to decrease consumption in animal models of alcohol dependence and in patients presenting alcohol dependence together with depressive-and or anxiety-like symptoms (Murphy et al, 1985;Naranjo and Sellers, 1989;Naranjo et al, 1994;Gulley et al, 1995;Maurel et al, 1999;Naranjo and Knoke, 2001;Kelai et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Gene Transcription Alterations Associated with Decrease of Ethanol Intake Induced by Naltrexone in the Brain of Wistar Rats

Martínez

Manzanares

2006

Neuropsychopharmacol

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Preclinical and clinical studies suggest that the administration of the opioid antagonist naltrexone decreases the intake of ethanol. However, the neuroplastic adaptations in the brain associated to reduction of ethanol consumption remains to be elucidated. The aim of the study was to identify gene transcription alterations underlying the attenuation of voluntary ethanol intake by administration of naltrexone in rats. Increasing doses of naltrexone (0.7 mg/kg, 4 days and 1.4 mg/kg/day, 4 days) to rats with acquired high preferring ethanol consumption (43.5 g of ethanol/kg/day) decreased voluntary ethanol intake (50%). Voluntary ethanol consumption altered mopioid receptor function in the cingulate cortex, caudate-putamen (CPu), nucleus accumbens core (Acb C) and shell (Acb S), the expression of tyrosine hydroxylase (TH) in the ventral tegmental area and substantia nigra, proenkephalin (PENK) in the piriform cortex, olfactory tubercle, CPu, Acb C and Acb S, ventromedial nucleus (VMN) and paraventricular nucleus (PVN) of the hypothalamus, corticotropin releasing factor (CRF) in PVN, cannabinoid CB 1 receptor (CB 1 -R) in the CPu, hippocampus and VMN, and serotonin transporter (5-HTT) in the dorsal and median raphe nuclei. The reduction of ethanol intake induced by naltrexone was associated with a blockade or significant reduction of the changes produced by ethanol in the expression of these genes in key regions related to drug dependence. These results point to a role for the m-opioid receptor, TH, PENK, CRF, CB 1 -R, and 5-HTT genes in specific brain regions in the modulation of neuroadaptative mechanisms associated to the decrease of ethanol intake induced by naltrexone. INTRODUCTIONAlcoholism is a serious health, social, and familiar problem of difficult solution produced by the conjunction of different complex causes that reflect the interaction of genetic, environmental, socio-cultural, and personal factors (Saatcioglu et al, 2006). In general, the main objective in the treatment of alcohol dependence is the maintenance of the abstinence and the reduction of seeking behavior to avoid relapse. The development of alcohol dependence is a slow process produced by continuous and repeated consumption of ethanol that results specially damaging to subjects presenting high impulsivity, low self-esteem, and sensation-seeking behavior. The vulnerability to develop any kind of problems related to ethanol becomes even higher in patients with certain psychiatric disorders such as phobias, attention-deficit hyperactive disorder or affective disorders (anxiety, depression, or bipolar disorder) (Hines et al, 2005). The reinforcing actions of ethanol are enhanced in these situations facilitating the progression to ethanol dependence. It has been proposed that consumption of ethanol stimulates dopamine neurons by acting directly on the nucleus accumbens and by disinhibiting GABA mesencephalic neurons projecting into the dopamine tegmental area (Spanagel and Weiss, 1999;Kienast and Heinz, 2006). Alterations in dopamine neurons ...

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Section: Discussionmentioning

confidence: 99%

Gene Transcription Alterations Associated with Decrease of Ethanol Intake Induced by Naltrexone in the Brain of Wistar Rats

Martínez

Manzanares

2006

Neuropsychopharmacol

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“…Since the recent identification of the polymorphism of the 5-HTT gene, search has focused on the influence of this polymorphism on different psychiatric disorders, including panic disorder [32], bipolar disorder [22,33,34], obsessive compulsive disorder [35], Alzheimer disease [36], schizophrenia [37], mood disorder [21,38], substance abuse [39,40] as well as ADHD [41][42][43][44][45][46].…”

Section: Discussionmentioning

confidence: 99%

Significance of Serotonin Transporter Gene 5-HTTLPR and Variable Number of Tandem Repeat Polymorphism in Attention Deficit Hyperactivity Disorder

Zoroğlu

Erdal²,

Alaşehirli³

et al. 2002

Neuropsychobiology

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The purpose of this study was to evaluate the relationship between attention deficit hyperactivity disorder (ADHD) and polymorphism of the two regions of the 5-HTT gene [variable number of tandem repeats (VNTR) and 5-HTTLRR] in a sample of Turkish children. Using the PCR technique, these polymorphisms were assessed in 71 patients with ADHD and 128 healthy controls. The 5-HTTLPR S/S genotype was significantly lower in the patients than in the controls (p = 0.018). Homozygous and heterozygous L variant predominated in the ADHD group. But the VNTR STin2.12/12 genotype was significantly less found in the patients than in the controls (p = 0.001). There was no significant difference between the frequency of the short (S), long, 10, and 12 alleles of both groups. The lack of an S/S variant of 5-HTTLPR polymorphism of the STin2.12/12 variant of VNTR polymorphism appears to be associated with an increased risk of ADHD.

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“…All twins were also typed for ABO, Rh and MNS blood groups by the Red Cross Blood Service in Brisbane. Genotypes for the 5-HTTLPR polymorphism were determined using the method described by Turker et al (1998), with primers 5k-GGCGTTGCCGCTCTGAATGCC and 5k-CAGGGGAGATCCTGGGAGAGGT. The PCR products were separated on 7 % polyacrylamide gel and visualized with ethidium bromide.…”

Section: Dna Extraction and Genotypingmentioning

confidence: 99%

The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression

et al. 2005

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High ethanol tolerance in young adults is associated with the low-activity variant of the promoter of the human serotonin transporter gene

Cited by 77 publications

References 13 publications

Gene Transcription Alterations Associated with Decrease of Ethanol Intake Induced by Naltrexone in the Brain of Wistar Rats

Gene Transcription Alterations Associated with Decrease of Ethanol Intake Induced by Naltrexone in the Brain of Wistar Rats

Significance of Serotonin Transporter Gene 5-HTTLPR and Variable Number of Tandem Repeat Polymorphism in Attention Deficit Hyperactivity Disorder

The relationship between stressful life events, the serotonin transporter (5-HTTLPR) genotype and major depression

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