ArticlePDF Available

Neurogenetic impairments of brain reward circuitry links to reward deficiency syndrome (RDS) as evidenced by genetic addiction risk score (GARS): A Case Study

Authors:

Abstract

Importantly, research from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)™ found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. Our laboratory has extensively published the neurogentics of brain reward systems with particular reference to genes related to dopaminergic function. In 1996, we coined “Reward Deficiency Syndrome” (RDS), used to describe behaviors found to have an association with gene-based hypodopaminergic function. Many subsequent studies have embraced RDS as a useful concept to help expand our understanding of Substance Use Disorder (SUD), process addictions, and other obsessive, compulsive and impulsive behaviors. Here, we illustrate the usefulness of the genetic testing of a panel of reward-related genes, the Genetic Addiction Risk Score (GARS) in only one case study. Interestingly, we were able to describe lifetime RDS behaviors in a recovery addict (17 years sober) blindly by just assessing resultant GARS data. We encourage further required studies in this important emerging field.
A preview of the PDF is not available
... RDS as a concept has been embraced in many subsequent studies to increase our understanding of addictions and other impulsive, compulsive, and obsessive behaviors. Interestingly, in one published study, Blum's group was able to detail lifetime RDS behaviors in a recovering addict (17 years sober) blindly by evaluating resultant Genetic Addiction Risk Score (GARS) data only [105]. It was hypothesized that genetic testing at an early age might be an effective preventive strategy to decrease or eliminate pathological behavioral and substance-seeking activities [106], providing further support of the disease model. ...
Article
Full-text available
Alcohol and other substance use disorders share comorbidity with other RDS disorders, i.e. a reduction in dopamine signaling within the reward pathway. RDS is a term that connects addictive, obsessive, compulsive, and impulsive behavioral disorders. An estimated 2 million individuals in the United States have opioid use disorder related to prescription opioids. It is estimated that the overall cost of the illegal and legally prescribed opioid crisis exceeds one trillion dollars. Opioid Replacement Therapy is the most common treatment for addictions and other RDS disorders. Even after repeated relapses, patients are repeatedly prescribed the same opioid replacement treatments. A recent JAMA report indicates that non-opioid treatments fare better than chronic opioid treatments. Research demonstrates that over 50 percent of all suicides are related to alcohol or other drug use. In addition to effective fellowship programs and spirituality acceptance, nutrigenomic therapies (e.g., KB220Z) optimize gene expression, rebalance neurotransmitters, and restore neurotransmitter functional connectivity. KB220Z was shown to increase functional connectivity across specific brain regions involved in dopaminergic function. KB220/Z significantly reduces RDS behavioral disorders and relapse in human DUI offenders. Taking a Genetic Addiction Risk Severity (GARS) test combined with a the KB220Z semi-customized nutrigenomic supplement effectively restores dopamine homeostasis. (WC 199).
... It is well-known reward center efficacy is necessary for brain, however, if neurogenesis influences all function of reward circuit is not well understood. It is not possible to say neurogenesis for proper reward center function is necessary since the reward center is influenced by many different mechanisms independent of neurogenesis (Park et al., 2014, Blum et al., 2013. ...
... Genetic Addiction Risk Score (GARS) screening for addiction and reward deficiency syndrome, is available to the public, from Geneus Health [32,33]. Genetic testing is an excellent tool for individualized treatment design and as prevention for the next generation [34,35]. ...
Article
Full-text available
Analytic review of research study results from psychology, addiction science, and interactive sciences like neurology, genetics, and epigenetics, implore psychology, psychiatry and addiction recovery treatment fields to enlarge their perspective, by considering underlying causal influence. The appropriate time to reconceptualize addiction for the practitioner world is now! Treatment protocol must expand beyond mitigation of the symptoms and address genetic, epigenetic and neurological causal influence. The science of Reward Deficiency Syndrome (RDS), offers a new phenotype for addiction, providing a common rubric for all obsessive, compulsive, and addictive behavioral patterns and contributes understanding of psychiatric genetics and/or causal influence of dopaminergic dysfunction in other co-occurring mental disorders. In consideration and review of the body of scientific knowledge, to successfully bridge the gap between science and practice, an integration of the sciences of addiction, and Reward Deficiency Syndrome must be achieved.
Article
Full-text available
Genetic Addiction Risk Severity (GARS) (Blum et al, 2014; Blum, Badgaiyan, Agan, Frantantonio, Simpatico, et al. 2015; Blum, Baron, Lott, Ponce, Siwicki, et al. 2019) screens for Reward Deficiency Syndrome (RDS) predisposition risk, for polymorphic variance within eleven alleles of the ten most common genes, in mental disorder. The RDS paradigm shift is concerned with treating the underlying neurogenetic and epigenetic challenges of dopaminergic dysfunction, as well as dysfunction in other neurotransmitter channels (Blum, Baron, McLaughlin, & Gold, 2020). Cutting edge psychiatric genomics recognizes that RDS is one preexisting causal influence for addiction (Tsermpini, Adla, & Patrinos, 2022). Consideration of preexisting neurogenetic challenges which affect low dopamine availability or epigenetic insults are not addressed in traditional old school, Minnesota Model twelve steps treatment modalities (Gilley, 2020), nor it is addressed in the current DSM 5th Edition (APA, 2013) (Gondre-Lewis, Bassey, & Blum, 2020). Scientists in the know are hopeful that RDS will be included in the next edition of the Diagnostic and Statistical Manual of Mental Disorders, as exponential increases in research studies from interactive sciences such as psychology, neurology, genetics and epigenetics have greatly enlarged perspective (Mancheno, Navas-Leon, Fernandez-Calderon, Gutierrez, Sanchez-Garcia, et al 2021). Sometimes progress is slow in funneling progressive cutting-edge applications from the research world into the practitioner world (CASA Columbia, 2012). Unfortunately, it is the patients who suffer, as the opioid overdose deaths of more than 100,000 this year alone, attest (Gupta, Bowirrat, Llanos Gomez, Baron, Elman, Giordano, et al 2022; Blum, Fried, Madigan, Giordano, Modestino, Steinbergy, et al 2017; Moran, Blum, Valdez Ponce, Lott, Gondre-Lewis, Badgaiyan, 2021). Not only have there been advancements in treatment models, from the Minnesota Model of the 1950’s, the Harm Reduction Model of the 1980’s (Paquette, Daughters, & Witkiewitz, 2022) and the Neurodevelopmental Model of addiction of the 2000’s (Leyton, 2012, 2014), there have been advancements in unifying theory. The evolution of the history of addiction recovery treatment would never be complete without mentioning the foundational dopamine depletion hypothesis (Dackis, & Gold, 1985; Diani, 2011; Volkow, Fowler, & Wang, 2002), which led to way to the current leading theory of Reward Deficiency Syndrome, which includes consideration of genetic (Dick, & Agrawal, 2008; Uhl, Liu, Walter, Hess, & Naiman, 2002) and epigenetic causal influences (Edwards, Roy, Boyett, Badgaiyan, Thanos, Baron, et al 2020; Vaillancourt, Ernst, Mash, & Turecki, 2017). RDS unifies all addictions, both substance and non-substance under a common rubric (Blum, Bowirrat, Braverman, Baron, Cadet, Kasmi, et al (2021). The Reward Deficiency Syndrome paradigm shift takes into consideration, underlying genetic, biological, physiological, and neurological mechanisms of the brain reward cascade (BRC). In this genomic era of addiction medicine, the new standard of excellence in addiction treatment begins genetic screening (Gilley, 2022 a, b, c). RDS treatment plans are built upon the foundational genetic and epigenetic causal influences (Gilley, 2021, b, c). RDS-Solution Focused Journal of Adolescent and Addiction Research How to cite this article: Elizabeth D. Gilley (2022). Stopping Addiction Before It Begins: The Future is Now. Journal of Adolescent and Addiction Research. 1(1); DOI: 10.0810/JAAR.2022/0002. Page 2 of 10 Introduction: Genetic screening is utilized in cancer prevention. Why not also utilize genetic screening for the prevention of mental health disorder, especially in children of addicted and/or mental health disorder diagnosed parents (Moberg, & Humphreys, 2016)? Why wait until addiction or mental health disorders manifest to treat them? Prevention is paramount to stopping the generation cycle from continuing in future generations. The Elle Foundation 100’s research case study series focuses upon our proband, Case Study #101 (Gilley 2022a) and her nuclear Reward Deficiency Syndrome family, Case Series #102 (Gilley, 2022 b) and Case Series #103 (Gilley, 2022c). Family members share polymorphic variances for pre-dispositional dopaminergic and serotonergic challenge. Addictive behavioral patterns, depression, mood disorders, and obesity are commonalities within this family sample. Decades of research show support for future manifestation of addictive behavioral patterns, and other mental health disorders, in children who experience trauma and other adverse environmental conditions. Those who experience serious trauma, are most likely to experience future manifestation of addictive behavioral patterns, and any of the other compulsive, obsessive, impulsive and personality disorders associated with Reward Deficiency Syndrome (Gilley, 2021, b, c). Genes alone do not create addiction, but rather it is the interactive influence of nature and nurture, both heredity and environmental factors which cause addiction (Gilley, 2018a). Genetic risk for RDS creates opportunity for early neurodevelopmental issues, such as Attention Deficit Disorder, Attention Deficit Hyperactivity Disorder (Gilley, 2018, c, d), and the Autism/Asperger Spectrum. Dopaminergic dysfunctions affect development over the entire lifespan. RDS has been proven to have correlation with all addictive behavioral expressions, both substance use and behavior process addictions. Later in life, RDS has been found to be correlational in dementias, such as Parkinson’s and Alzheimer’s Disease. See Figure 1- Lifespan Timeline for RDS phenomenon. RDS is enlarged unifying theory, linking all dopaminergic deficiency addictions, both substance and behavior (Blum, Febo, Badgaiyan, Demetrovics, Simpatico, et al. 2017), with dopamine deficiency mental health disorders, which include obsessive compulsive, impulsive and personality disorders (Blum, & Braverman, 2000). Since Reward Deficiency Syndrome phenotypes run in families (Blum, Chen, Oscar�Berman, Chen, Lubar et al. 2011), the Elle Foundation recommends genetic testing not only for the children of addicts, but for all family members (Blum, Steinberg, Gondre-Lewis, Simpatico, Ceccanti, Steinberg, 2021). See Figure 2- Reward Deficiency Syndrome Behaviors, curtesy of GeneusHealth.com. Figure 2: Brief Intervention (RDS-SFBI) administers bio-neuro-psychological therapy which assists the client in achieving dopamine homeostasis (Gilley, 2019). Since RDS effects the individual over the entire lifespan, it should be treated as a front-line modality (Blum, Raza, Schultz, Jalali, Green, Brewer, et al 2021), by primary physicians, and teams of RDS specialists (Gilley, Bowirrat, Gupta, Giordano, Dennen, Braverman, Badgaiyan, McLaughin, Baron, & Blum, 2022). Keywords: Reward Deficiency Syndrome, Genetic Addiction Risk Severity (GARS), Addiction Prevention
Article
Both anhedonia and craving are common among patients with opioid use disorder (OUD), and are associated with vulnerability to relapse. Although these constructs are theoretically linked relatively few studies have examined them together. In the current study, recently withdrawn patients (N = 71) in residential treatment for prescription OUD underwent a cue reactivity paradigm while being monitored with functional near-infrared spectroscopy (fNIRS). Patients also self-reported symptoms of anhedonia via the Snaith-Hamilton Pleasure Scale (SHAPS), while smartphone-based ecological momentary assessments (EMA) were used to measure craving levels. On average, lower right prefrontal cortex (PFC) activity in response to positive social stimuli was associated with higher craving (β = -2.87; S.E. = 1.23; p = 0.02). Self-reported anhedonia moderated the association between PFC activity and craving (β = -1.02; S.E. = 0.48; p = 0.04), such that patients with two or more anhedonic symptoms had a significant and stronger negative association between PFC activation to hedonically positive images and craving, compared to patients with fewer than two anhedonic symptoms, among whom the association was not significant. This finding provides evidence that higher levels of anhedonia among patients in residential treatment for OUD are associated with a stronger link between lower PFC response to positive social experiences and higher levels of craving, potentially increasing overall vulnerability to relapse.
Article
Full-text available
Both quantitative and qualitative observation are used for statistical analysis of the Reward Deficiency Syndrome phenotype, neurogenetic predisposition, for addiction and mental disorder endotypes, in this level 4 evidence, case series. In continuation of the Elle Foundation, 100 research series, Case Series 103 builds upon Case Study 101, in which we introduced the longitudinal study of our proband[1-2]; and Case Series 102[3] in which we compared biological sisters’ underlying neurogenetic predisposition for Reward Deficiency Syndrome (RDS). Case study series 103 observes a four generational family for polymorphic gene variances which predispose risk for Reward Deficiency Syndrome (RDS)[4-5] and compares reported lifespan experience of Diagnostic Statistical Manual of Mental Disorder (DSM).[6] Data was collected using personal interview, self-report, personality testing, the RDSQ29[7] and Genetic Addiction Risk Severity (GARS).[8] Result findings support the hypothesis that the proband’s polymorphic variances are shared by other family members, adding to the international body of evidence that RDS is a family disease, which should be treated as a frontline modality[9], on a continuum of care[10- 11], beginning with Primary Physicians.[12] GARS testing for SUD patients, family members and the next generation of children is advised. KEYWORDS: Reward Deficiency Syndrome, Genomic Addiction Medicine, Preci
Research
Full-text available
In the Elle Foundation, Case Study 102, the participant was given a Reward Deficiency Syndrome Symptom Checklist, in which she was asked about her dopamine deficiency symptom experience. The Reward Deficiency Syndrome Questionnaire (RDSQ-29)[1] was administered and the GARS, Genetic Addiction Risk Severity test [2] given in follow up. The GARS determined her predisposition for neurological challenge, in both dopaminergic and serotonergic channels, and her RDS phenotype [3]. In this retrospective, observational study, it is easy to discern the predictive value of the GARS, in 2020 hindsight, to determine predisposition for selective choice of various addictive behavioral paths to boosting dopamine deficiency [4] This participant's life experience is used to illustrate the new Reward Deficiency Syndrome paradigm, including the therapeutic value of the GARS [5], RDS Solutions for her phenotype (Blum et al., 2011) and RDS Solution Focused Brief Therapy (RDS-SFBT) [6], which is psychological education for overcoming dopamine deficiency, to achieve and maintain dopamine homeostasis [7].
Article
Full-text available
Enlarged perspective of drug seeking motivational effects of dopamine deficiency and/or deregulation, in the brain's reward cascade system provide new understanding of the underlying addiction syndrome called Reward Deficiency Syndrome (RDS). Reward Deficiency Syndrome Solutions™(RDSS) have been used to successfully treat a Substance Use Disorder (SUD) treatment resistant patient. As an alternative to repetitive Substance Use Disorder treatment, the new Reward Deficiency Syndrome paradigm was introduced to the subject, through RDS Solution Focused Brief Therapy (RDS-SFBT), facilitating increased awareness and self-efficacy, for autonomy in symptom management. A reward deficiency syndrome treatment plan (Gilley, 2018d) was developed, based upon findings from Genetic Addiction Risk Severity (GARS) (Blum & Chen, 2011) analysis. Pre-existing neurogenic challenge, due to polymorphic genetic variances effecting dopaminergic and serotonergic systems were discovered. Epigenetic response, resulting from the brains over correction of self-induced dopamine surge, resulted in further dopaminergic insult. Intervention for correction of neurological challenge was meet with an enthusiasm for self-empowerment, motivating the client to become increasingly engaged in her own recovery. RDS Solution Focused Brief Therapy (RDS-SFBT) (Gilley, 2019) and the RDS Severity of Symptom scale (RDS-SOS) were introduced to assist in the psychoeducation of the RDS paradigm, to teach skill for achieving dopamine homeostasis, and to gage intensity of relapse symptomology. We observed the subject over a period of months, documenting her challenge and improvement, as she learned to achieve and maintaine dopamine homeostasis, through various wellness practices. The Elle Foundation Case Study 101 documents the positive effects of Reward Deficiency Syndrome science and its solutions, to facilitate transition from active addiction, and/or neurological instability, to abstinence, maintenance, self-efficacy, self-actualization and thriving (Gilley, 2017).
Article
Full-text available
Over years, the regular use of cannabis has substantially increased among young adults, as indicated by the rise in cannabis use disorder (CUD), with an estimated prevalence of 8. 3% in the United States. Research shows that exposure to cannabis is associated with hypodopaminergic anhedonia (depression), cognitive decline, poor memory, inattention, impaired learning performance, reduced dopamine brain response-associated emotionality, and increased addiction severity in young adults. The addiction medicine community is increasing concern because of the high content of delta-9-tetrahydrocannabinol (THC) currently found in oral and vaping cannabis products, the cognitive effects of cannabis may become more pronounced in young adults who use these cannabis products. Preliminary research suggests that it is possible to induce 'dopamine homeostasis,' that is, restore dopamine function with dopamine upregulation with the proposed compound and normalize behavior in chronic cannabis users with cannabis-induced hypodopaminergic anhedonia (depression) and cognitive decline. This psychological, neurobiological, anatomical, genetic, and epigenetic research also could provide evidence to use for the development of an appropriate policy regarding the decriminalization of cannabis for recreational use.
Article
Full-text available
INTRODUCTION DISCUSSION OF NEUROGENETIC AND EPIGENETIC RESEARCH ADVANCEMENT IN ADDICTION MEDICINE Approximately 50 years of research have led to new understanding and a new phenotype for impulsive, addictive and compulsive behavioral expression with the successful evidence based concept of Reward Deficiency Syndrome (Blum, Braverman, Holder, Lubar, Miller, Monastro, Commings et al, 2000) which is linking all addictions under a common rubric (Blum, Febo, McLaughin, Cronje, Han et al, 2014), and changing the recovery landscape. Although Kenneth Blum is accredited with first coining the phrase in 1995 (Febo, Blum, Badgaiyan, Baron, Thanos, Colon-Perez, et al, 2017), literally thousands of research scientists have contributed to the advancement of the field of the neurogenetics of addiction (Ducci & Goldman, 2012). There is no debate on the doctoral and post-doctoral levels of neuroscience. Some are informed. Others are not. The evolution of addiction science has revealed a new phenotype. “RDS is the disease, [and] addiction it’s symptom” (Gilley, 2018, p. 161; Smith. 2012).
Article
Full-text available
Work from our laboratory in both in-patient and outpatient facilities utilizing the Comprehensive Analysis of Reported Drugs (CARD)(™) found a significant lack of compliance to prescribed treatment medications and a lack of abstinence from drugs of abuse during active recovery. This unpublished, ongoing research provides an impetus to develop accurate genetic diagnosis and holistic approaches that will safely activate brain reward circuitry in the mesolimbic dopamine system. This editorial focuses on the neurogenetics of brain reward systems with particular reference to genes related to dopaminergic function. The terminology "Reward Deficiency Syndrome" (RDS), used to describe behaviors found to have an association with gene-based hypodopaminergic function, is a useful concept to help expand our understanding of Substance Use Disorder (SUD), process addictions, and other obsessive, compulsive and impulsive behaviors. This editorial covers the neurological basis of pleasure and the role of natural and unnatural reward in motivating and reinforcing behaviors. Additionally, it briefly describes the concept of natural dopamine D2 receptor agonist therapy coupled with genetic testing of a panel of reward genes, the Genetic Addiction Risk Score (GARS). It serves as a spring-board for this combination of novel approaches to the prevention and treatment of RDS that was developed from fundamental genomic research. We encourage further required studies.
Article
Full-text available
This article will touch on theories, scientific research and conjecture about the evolutionary genetics of the brain function and the impact of genetic variants called polymorphisms on drug-seeking behavior. It will cover the neurological basis of pleasure-seeking and addiction, which affects multitudes in a global atmosphere where people are seeking "pleasure states".
Article
Full-text available
The nucleus accumbens, a site within the ventral striatum, plays a prominent role in mediating the reinforcing effects of drugs of abuse, food, sex, and other addictions. Indeed, it is generally believed that this structure mandates motivated behaviors such as eating, drinking, and sexual activity, which are elicited by natural rewards and other strong incentive stimuli. This article focuses on sex addiction, but we hypothesize that there is a common underlying mechanism of action for the powerful effects that all addictions have on human motivation. That is, biological drives may have common molecular genetic antecedents, which if impaired, lead to aberrant behaviors. Based on abundant scientific support, we further hypothesize that dopaminergic genes, and possibly other candidate neurotransmitter-related gene polymorphisms, affect both hedonic and anhedonic behavioral outcomes. Genotyping studies already have linked gene polymorphic associations with alcohol and drug addictions and obesity, and we anticipate that future genotyping studies of sex addicts will provide evidence for polymorphic associations with specific clustering of sexual typologies based on clinical instrument assessments. We recommend that scientists and clinicians embark on research coupling the use of neuroimaging tools with dopaminergic agonistic agents to target specific gene polymorphisms systematically for normalizing hyper- or hypo-sexual behaviors.
Article
We have advocated the idea of agonist therapy for treating cocaine addiction. This strategy involves administration of stimulant-like medications (eg, monoamine releasers) to alleviate withdrawal symptoms and prevent relapse. A major limitation of this approach is that many candidate medicines possess significant abuse potential because of activation of mesolimbic dopamine (DA) neurons in central nervous system reward circuits. Previous data suggest that serotonin (5-HT) neurons can provide an inhibitory influence over mesolimbic DA neurons. Thus, it might be predicted that the balance between DA and 5-HT transmission is important to consider when developing medications with reduced stimulant side effects. In this article, we discuss several issues related to the development of dual DA/5-HT releasers for the treatment of substance use disorders. First, we discuss evidence supporting the existence of a dual deficit in DA and 5-HT function during withdrawal from chronic cocaine or alcohol abuse. Then we summarize studies that have tested the hypothesis that 5-HT neurons can dampen the effects mediated by mesolimbic DA. For example, it has been shown that pharmacological manipulations that increase extracellular 5-HT attenuate stimulant effects produced by DA release, such as locomotor stimulation and self-administration behavior. Finally, we discuss our recently published data about PAL-287 (naphthylisopropylamine), a novel non-amphetamine DA-/5-HT-releasing agent that suppresses cocaine self-administration but lacks positive reinforcing properties. It is concluded that DA/5-HT releasers might be useful therapeutic adjuncts for the treatment of cocaine and alcohol addiction, obesity, and even attention deficit disorder and depression.
Article
To the Editor.— The rationale, design, and biologic significance of association studies of genetic markers in disease need to be understood to evaluate claims for the role of a dopamine receptor gene in alcoholism.1A DNA variant or restriction fragment length polymorphism for a dopamine-2 receptor gene has been described.2 The frequencies of allele 1 and allele 2 were 0.24 and 0.76, respectively, in a normal population. The probe used and extensive knowledge about the sites of restriction fragment length polymorphisms in DNA suggest that this alteration affects noncoding DNA. Such DNA markers are frequent and usually have no biologic function. Blum et al1 used this probe in 35 brain DNA specimens from nonalcoholics and found allele 1 and 2 frequencies of 0.13 and 0.87, respectively. In contrast, among brain samples from 35 alcoholics the frequencies of allele 1 and allele 2 were 0.37 and 0.63, respectively. Based
Article
In a blinded experiment, the authors report the first allelic association of the dopamine Dâ receptor gene in alcoholism. From 70 brain samples of alcoholics and nonalcoholics, DNA was digested with restriction endonucleases and probed with a clone that contained the entire 3â² coding exon, the polyadenylation signal, and approximately 16.4 kilobases of noncoding 3â² sequence of the human dopamine Dâ receptor gene (λhD2G1). In the present samples, the presence of A1 allele of the dopamine Dâ receptor gene correctly classified 77% of alcoholics, and its absence classified 72% of nonalcoholics. The polymorphic pattern of this receptor gene suggests that a gene that confers susceptibility to at least one form of alcoholism is located on the q22-q23 region of chromosome 11.
Article
The gene encoding the dopamine D2 receptor (DRD2) has been suggested as a candidate gene for several mental disorders. We previously described the cloning and chromosomal mapping (to 11q22–q23) of a human DRD2 gene as well as its use for the detection of a two-allele TaqI RFLP with a minor allele frequency of 0.24, corresponding to a PIC of 0.30. Family linkage studies utilizing DRD2 would be facilitated if the PIC of the DRD2 locus were increased. To this end, we have used additional phage and cosmid clones in the vicinity of DRD2 to identify a new two-allele TaqI RFLP as well as a TG microsatellite polymorphism with a PIC of 0.62. We report localizations of the three polymorphisms on the restriction map of the DRD2 locus. The TaqI RFLPs are in apparent linkage equilibrium with the microsatellite, yielding a highly informative compound marker locus with a PIC of 0.76.
Article
The mechanism(s) underlying predisposition to alcohol abuse are poorly understood but may involve brain dopamine system(s). Here we used an adenoviral vector to deliver the dopamine D2 receptor (DRD2) gene into the nucleus accumbens of rats, previously trained to self-administer alcohol, and to assess if DRD2 levels regulated alcohol preference and intake. We show that increases in DRD2 (52%) were associated with marked reductions in alcohol preference (43%), and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. In addition, this DRD2 overexpression similarly produced significant reductions in ethanol non-preferring rats, in both alcohol preference (16%) and alcohol intake (75%). This is the first evidence that overexpression of DRD2 reduces alcohol intake and suggests that high levels of DRD2 may be protective against alcohol abuse.