Serotonin transporter promoter polymorphism and dopaminergic sensitivity in alcoholics

被引:5
作者
Budde, Henning [4 ]
Sander, Thomas [5 ]
Wernicke, Catrin [6 ]
Mueller, Anett [7 ]
Gallinat, Juergen [3 ]
Schmidt, Lutz G. [2 ]
Smolka, Michael N. [1 ]
机构
[1] Tech Univ Dresden, Sect Syst Neurosci, Dept Psychiat & Psychotherapy, D-01187 Dresden, Germany
[2] Johannes Gutenberg Univ Mainz, Dept Psychiat & Psychotherapy, D-55131 Mainz, Germany
[3] Charite, Dept Psychiat & Psychotherapy, D-13353 Berlin, Germany
[4] Humboldt Univ, Dept Movement & Training Sci, Inst Sport Sci, D-10115 Berlin, Germany
[5] Univ Cologne, Cologne Ctr Gen, D-50674 Cologne, Germany
[6] Charite, Sect Clin Neurobiol, Dept Psychiat & Psychotherapy, D-14050 Berlin, Germany
[7] Tech Univ Dresden, Dept Psychol, D-01069 Dresden, Germany
关键词
Serotonin transporter; Dopamine; Alcohol; Apomorphine; Growth hormone; GROWTH-HORMONE RESPONSE; RECEPTOR AVAILABILITY; NICOTINE DEPENDENCE; GENOTYPE; BINDING; MECHANISMS; ETHANOL; RELAPSE; ASSOCIATION; EXPRESSION;
D O I
10.1007/s00702-009-0331-9
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
The central serotonin (5-HT) system plays an important role in the rewarding and addictive properties of alcohol by a direct activation of the mesolimbic dopamine (DA) system. An insertion/deletion (L/S) promoter polymorphism (5-HTTLPR) of the 5-HT transporter (5-HHT) gene (SLC6A4) has been shown to influence transcriptional activity. It is predicted that reduced transynaptic 5-HT neurotransmission in alcoholics with the L/L genotype of 5-HTTLPR would result in a change in DA function compared to the S/S genotype. Thus the present study has tested whether dopaminergic sensitivity is influenced by the 5-HTTLPR genotype. Dopaminergic sensitivity, 5-HTTLPR genotype and smoking status were assessed in 121 alcoholics. Dopaminergic sensitivity as an indicator of the functional state of the dopaminergic system was measured by the amount of growth hormone (GH) secretion after subcutaneous administration of apomorphine (APO, 0.01 mg/kg). 5-HTTLPR genotype was significantly associated with dopaminergic sensitivity (P = 0.004) explaining 9.2% of the variance of GH response. Subjects homozygous for the L allele (with high 5-HTT expression) showed the lowest GH response, whereas those homozygous for the S allele (with low 5-HTT expression) showed the highest GH response (this was intermediate in heterozygous participants). Furthermore smoking was associated with a significantly reduced GH response (P = 0.006). Our findings indicate that the postsynaptic dopaminergic sensitivity is influenced by the 5-HTTLPR genotype. It is hypothesized that the reduction of sensitivity of the central DA receptors in alcoholics with the L/L genotype might be due to their higher vulnerability to the neurotoxic effects of chronic alcohol consumption than the S carriers.
引用
收藏
页码:133 / 138
页数:6
相关论文
共 31 条
[1]   Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission [J].
Alex, K. D. ;
Pehek, E. A. .
PHARMACOLOGY & THERAPEUTICS, 2007, 113 (02) :296-320
[2]   Pharmacokinetic-pharmacodynamic study of apomorphine's effect on growth hormone secretion in healthy subjects [J].
Aymard, G ;
Berlin, I ;
de Brettes, B ;
Diquet, B .
FUNDAMENTAL & CLINICAL PHARMACOLOGY, 2003, 17 (04) :473-481
[3]   Accumbal dopamine overflow after ethanol: Localization of the antagonizing effect of mecamylamine [J].
Blomqvist, O ;
Ericson, M ;
Engel, JA ;
Soderpalm, B .
EUROPEAN JOURNAL OF PHARMACOLOGY, 1997, 334 (2-3) :149-156
[4]   Alcohol promotes dopamine release in the human nucleus accumbens [J].
Boileau, I ;
Assaad, JM ;
Pihl, RO ;
Benkelfat, C ;
Leyton, M ;
Diksic, M ;
Tremblay, RE ;
Dagher, A .
SYNAPSE, 2003, 49 (04) :226-231
[5]   Apomorphine-induced growth hormone response is attenuated by ethanol but not dextromethorphan [J].
Budde, Henning ;
Zimmermann, Ulrich S. ;
Steffin, Birgit ;
Rommelspacher, Hans ;
Schmidt, Lutz G. ;
Smolka, Michael N. .
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2007, 31 (01) :100-103
[6]   Reduced dopamine D1 receptor binding in the ventral striatum of cigarette smokers [J].
Dagher, A ;
Bleicher, C ;
Aston, JAD ;
Gunn, RN ;
Clarke, PBS ;
Cumming, P .
SYNAPSE, 2001, 42 (01) :48-53
[7]  
DETTLING M, 1995, AM J PSYCHIAT, V152, P1317
[8]  
DICHIARA G, 1988, P NATL ACAD SCI USA, V85, P5274
[9]   Association of low striatal dopamine D2 receptor availability with nicotine dependence similar to that seen with other drugs of abuse [J].
Fehr, Christoph ;
Yakushev, Igor ;
Hohmann, Nina ;
Buchholz, Hans-Georg ;
Landvogt, Christian ;
Deckers, Hanna ;
Eberhardt, Alexandra ;
Klager, Marie ;
Smolka, Michael N. ;
Scheurich, Armin ;
Dielentheis, Thomas ;
Schmidt, Lutz G. ;
Roesch, Frank ;
Bartenstein, Peter ;
Gruender, Gerhard ;
Schreckenberger, Mathias .
AMERICAN JOURNAL OF PSYCHIATRY, 2008, 165 (04) :507-514
[10]  
Greenberg BD, 1999, AM J MED GENET, V88, P83, DOI 10.1002/(SICI)1096-8628(19990205)88:1<83::AID-AJMG15>3.0.CO