The Taq A1 variant of the human DRD2 gene has been associated with drug addiction, some forms of severe alcoholism, and other impulsive, addictive behaviours.
Since the cannabinoid system is part of the reward pathway we examined the hypothesis that genetic variants of the CNR1 gene might be associated with susceptibility to alcohol or drug dependence.
In our prior study we observed a significant association between homozygosity for the > or = alleles of a microsatellite polymorphism of cannabinoid receptor genes (CNR1) and drug dependence.
In addition, the genetically altered mice offer a unique model to test the specificity and selectivity of dopamine transporter-acting drugs and may provide important new concepts related to the clinical and social implications of conditions such as Parkinson's disease, schizophrenia, and drug addiction.
OPRM1 alleles, genotypes and haplotypes from three psychiatrically characterized population samples (US Caucasian [USC, n=100], Finnish Caucasian [FC, n=324] and Southwestern American Indian [SAI, n=367]), were used to perform association and sib-pair linkage analyses with alcohol and drug dependence diagnoses.
Progress in 5-HTT gene inactivation studies are also changing views of the relevance of adaptive 5-HT uptake function in brain development and plasticity as well as processes underlying drug dependence and neurodegeneration.
Although obtained in a sample of limited size, these results suggest that the DRD3 gene may have a role in drug dependence susceptibility in individuals with high sensation-seeking scores.
Consequently, the present study examined the association of a polymorphic (CA)n repeat at the OPRM1 locus (the gene coding for the mu opioid receptor) to alcohol or drug dependence in 320 Caucasian and 108 African-American substance-dependent or control subjects.
Because positive association between DRD2 alleles and alcohol and/or drug dependence has been reported only in populations of European ancestry, we limited the present study to European Americans (EAs).
Further, the Canadian Native Indian, South-east Asian Canadian and Caucasian Canadian groups were stratified by alcohol and nicotine dependence (as measured by DSM-IV criteria) to examine the potential association of CYP2E1*1D with drug dependence.
Our findings suggest that the low-activity 3-repeat allele of the MAO-A promoter polymorphism confers increased susceptibility to antisocial-violent behavior and aggressiveness, rather than drug dependence per se, in heroin-dependent males.
The presentations were (1) Ethanol Modulation of CREB: Role in Dependence and Withdrawal, by Fulton Crews; (2) Effects of D1 Dopamine Receptor Activation During Withdrawal From Chronic Morphine: Enhanced CREB Activation and Decreased Conditioned Place Aversion, by Elena H. Chartoff; (3) CREB-Haplodeficient Mice: Role in Anxiety and Alcohol-Drinking Behaviors, by Subhash C. Pandey; and (4) A Role for CREB in Stress and Drug Addiction, by Julie A. Blendy.
Increasing evidence suggests that differences in Oprm1 gene sequences affect the amount of Oprm1 mRNA and sensitivity to opiates, and >100 polymorphisms have been identified in the human OPRM1 gene, some of which are related to vulnerability to drug dependence in some populations.
Homer proteins are involved in the functional assembly of postsynaptic density proteins at glutamatergic synapses and are implicated in learning, memory and drug addiction.
Genetic variants of OPRM1 have been implicated in predisposition to drug addiction, in particular the single nucleotide polymorphism A118G, leading to an N40D substitution, with an allele frequency of 10-32%, and uncertain functions.
Our findings suggest that the 9-repeat allele of the DAT polymorphism confers increased susceptibility to antisocial - violent behaviour and aggressiveness, rather than drug dependence per se in heroin-dependent males.
Using rigorous study designs that account for possible population stratification, these findings confirm and extend our original observations indicating that variation at ADH4 predisposes to alcohol and drug dependence.