Neurobiology Of Addiction Research Articles

Peter W. Kalivas: To the tetrapartite synapse and beyond – A pathway for new drug targets to treat behavioral disorders

Peter Kalivas stands as a pioneering architect in our understanding of addiction neuroscience, having transformed our knowledge of how substances of abuse reshape brain circuits and cellular function. Over four decades, his groundbreaking research has illuminated the fundamental mechanisms underlying substance use disorders, mainly through his seminal discoveries of glutamate's critical role in addiction and his innovative work on the “tetrapartite synapse” – revealing how astroglia and the extracellular matrix regulate addictive behaviors. With over 400 publications and eight edited volumes, his research has revolutionized our conceptual framework for treating addiction by identifying novel therapeutic targets beyond traditional neurotransmitter systems. After receiving his PhD in Pharmacology from the University of Washington and completing postdoctoral training at the University of North Carolina, Dr. Kalivas built an extraordinary scientific legacy at Washington State University and then as the founding Chair of Neuroscience at the Medical University of South Carolina. There, he established a world-renowned research program that has trained generations of addiction scientists while developing innovative approaches to understanding stress, PTSD, and substance use disorders. Now serving as Distinguished University Professor, he continues to pioneer new frontiers in addiction neuroscience through his work on neural circuits and synaptic plasticity. In this Genomic Press Interview, Dr. Kalivas shares insights from his remarkable journey investigating the neurobiology of addiction and his vision for the field's future.

Imaging Dopamine Modulation in Brain Acute Slices for Cocaine Addiction Study with Near-Infrared Carbon Nanotube Sensors

Drug addiction is a pressing issue in modern American society that demands thorough research into its mechanisms. Cocaine locomotor sensitization is a well-established model for understanding the physiological effects of cocaine abuse. Previous studies have established loss of dopamine D2 autoreceptors in striatal tissue as a consequence of locomotor sensitization, yet how these differences in autoreceptor expression affect dopamine signaling remains unclear. Herein, we utilized non-genetically encoded near-infrared fluorescent nanosensors based on carbon nanotubes to image dopamine modulation in live acute coronal brain slices. By leveraging dopamine D2 receptor agonists along with the dopamine nanosensor, we developed a method to identify changes in density of functional D2 autoreceptors and dopamine signaling aberrations that accompany addiction, at the level of individual dopamine synapses. We apply the method to compare changes in D2 autoreceptor activity in the Nucleus Accumbens core in cocaine sensitized and saline (control) mice after prolonged cocaine exposure (5 days). Our preliminarily data indicates the decrease in the number of D2 autoreceptor in cocaine sensitized mice, consistent with the previous studies, and suggests that it leads to higher level of dopamine signaling. Furthermore, we confirm dopamine signaling changes by application of D2 Agonists (quinpirole) are from loss of individual dopamine release sites rather than changes in the quantity of dopamine released, or changes in dopamine reuptake kinetics. Our study provides a route to understand the changes in neuromodulation that underlie the neurobiology of addiction and other dopamine-centric neurological conditions.

Potential Involvement of Apelin/APJ System in Addiction and Neuroprotection Against Drugs of Abuse.

Addiction, characterized by compulsive drug-seeking behavior and impaired self-control, remains a significant public health concern. Understanding the neurobiology of addiction is crucial for identifying novel therapeutic targets and further developing effective treatments. Recently, the apelin/APJ system, an emerging signaling pathway, has attracted attention for its involvement in various neuropsychiatric disorders. The cross-talk between the apelin/APJ system and hypothalamic mu opioid signaling, as well as its heterodimerization with kappa opioid receptors (KORs), supports the potential relevance of this system to addiction. Moreover, several protective effects of apelin against various addictive substances, including methamphetamine, morphine, and alcohol, underscore the need for further investigation into its role in substance use disorder. Understanding the contribution of the apelin/APJ system in addiction may offer valuable insights into the underlying neurobiology and pave the way for novel therapeutic interventions in substance use disorders. This review provides a concise overview of the apelin/APJ system, emphasizing its physiological roles and highlighting its relevance to addiction research.

Unraveling The Neurobiology of Addiction: Insights into Mechanisms and Therapeutic Avenues

Unraveling The Neurobiology of Addiction: Insights into Mechanisms and Therapeutic Avenues

Leveraging neuroscience education to address stigma related to opioid use disorder in the community: a pilot study.

Opioid use disorder (OUD) and overdose deaths are a public health crisis. One contributing factor is stigma towards people who use opioids. We developed and conducted a public-facing, half-day educational event designed to challenge misperceptions about OUD from a contemporary neuroscience perspective. Participants engaged with three different resources on the neurobiology of addiction, and, at the end of the event, they rated its effectiveness. We also collected and compared pre- and post-event composite OUD stigma scales. Participants rated our approach and the overall event as highly effective. Additionally, OUD stigma scores were lower immediately following the event, and this decrease was primarily driven by decreased internalized stigma. Here, we demonstrate an effective proof-of-concept that an accessible, public-facing, neuroscience education event may reduce OUD stigma in the community.

Application of Covalent Organic Framework-Based Solid-Phase Microextraction for Efficient and Direct Analysis of Neurotransmitters in the Striatum of Nicotine-Addicted mice

This study developed and validated a novel solid-phase microextraction (SPME) method based on covalent organic framework (COF) for the simultaneous analysis of 10 neurotransmitters (NTs) in mice brain tissue using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The synthesized COF was utilized as SPME fiber coating, exhibited a suitable pore size and macromolecule exclusion capability, ensuring excellent thermal stability and high adsorption efficiency for NTs. This allowed direct extraction from brain homogenates, eliminating the need for protein precipitation. And the COF-based SPME fiber exhibited good reusability throughout eight successive recycling cycles. The SPME-UHPLC method demonstrated excellent linearity (correlation coefficients > 0.99), low intra- and inter-day precision (RSDs ≤ 9.5 % and ≤ 10.6 %, respectively), and acceptable matrix effects (ranging 84.3 % to 117.3 %). The developed method was then applied to analyze NTs in the striatum of nicotine-addicted mice, and the statistical analysis revealed significant shifts in the concentrations of dopaminergic, serotonergic, glutamatergic, addiction and deepened the understanding of addiction's neurobiology. This method offers a sensitive and efficient approach for extracting polar NT analytes in complex matrices, profiling NT alterations linked to addiction, and holds potential for early detection and treatment of addiction disorders. It could contribute significantly to addiction neurobiology and neurological disease research.

Physical Exercise Promotes Beneficial Changes on Neurotrophic Factors in Mesolimbic Brain Areas After AMPH Relapse: Involvement of the Endogenous Opioid System.

Addiction is a serious public health problem, and the current pharmacotherapy is unable to prevent drug use reinstatement. Studies have focused on physical exercise as a promising coadjuvant treatment. Our research group recently showed beneficial neuroadaptations in the dopaminergic system related to amphetamine-relapse prevention involving physical exercise-induced endogenous opioid system activation (EXE-OS activation). In this context, additional mechanisms were explored to understand the exercise benefits on drug addiction. Male rats previously exposed to amphetamine (AMPH, 4.0mg/kg) for 8days were submitted to physical exercise for 5weeks. EXE-OS activation was blocked by naloxone administration (0.3mg/kg) 5min before each physical exercise session. After the exercise protocol, the rats were re-exposed to AMPH for 3days, and in sequence, euthanasia was performed and the VTA and NAc were dissected. In the VTA, our findings showed increased immunocontent of proBDNF, BDNF, and GDNF and decreased levels of AMPH-induced TrkB; therefore, EXE-OS activation increased all these markers and naloxone administration prevented this exercise-induced effect. In the NAc, the same molecular markers were also increased by AMPH and decreased by EXE-OS activation. In this study, we propose a close relation between EXE-OS activation beneficial influence and a consequent neuroadaptation on neurotrophins and dopaminergic system levels in the mesolimbic brain area, preventing the observed AMPH-relapse behavior. Our outcomes bring additional knowledge concerning addiction neurobiology understanding and show that EXE-OS activation may be a potential adjuvant tool in drug addiction therapy.

A Brief Overview of the Neuropharmacology of Opioid Addiction.

The world is in the midst of an opioid crisis. Nearly 92,000 persons in the U.S. alone died from illicit drugs and prescription opioids in 2020 [1]. This number does not include the countless other individuals who die as a result of the violent crime that accompanies the illicit drug trade. To address this crisis, we need to appreciate aspects of drug addiction. The goal of this brief review is to highlight some major facets of addiction neurobiology, focused on opioids, to provide a basic understanding of the research and terminology encountered in more detailed in-depth articles and discussions on addiction.

The Genetically Informed Neurobiology of Addiction (GINA) model.

Addictions are heritable and unfold dynamically across the lifespan. One prominent neurobiological theory proposes that substance-induced changes in neural circuitry promote the progression of addiction. Genome-wide association studies have begun to characterize the polygenic architecture undergirding addiction liability and revealed that genetic loci associated with risk can be divided into those associated with a general broad-spectrum liability to addiction and those associated with drug-specific addiction risk. In this Perspective, we integrate these genomic findings with our current understanding of the neurobiology of addiction to propose a new Genetically Informed Neurobiology of Addiction (GINA) model.

Cingulate cortical thickness in cocaine use disorder: mediation effect between early life stress and cocaine consumption.

The cingulate gyrus is implicated in the neurobiology of addiction, such as chronic cocaine consumption. Early life stress (ELS) is an important moderator of cocaine use disorder (CUD). Therefore, we investigated the effect of CUD on cingulate cortical thickness and tested whether a history of ELS could influence the effects of CUD. Participants aged 18-50 years (78 with CUD due to crack cocaine consumption and 53 healthy controls) underwent magnetic resonance imaging and the cingulate thickness (rostral anterior, caudal anterior, posterior, and isthmus regions) was analysed. The clinical assessment comprised the Childhood Trauma Questionnaire (CTQ) and the Addiction Severity Index. Group comparisons adjusting by sex, age, and education were performed. Mediation models were generated where lifetime cocaine use, CTQ score, and cortical thickness corresponded to the independent variable, intermediary variable, and outcome, respectively. Group comparisons revealed significant differences in six out of eight cingulate cortices, showing lower thickness in the CUD group. Furthermore, years of regular cocaine use was the variable most associated with cingulate thickness. Negative correlations were found between CTQ scores and the isthmus cingulate (right hemisphere), as well as with the rostral anterior cingulate (left hemisphere). In the mediation analysis, we observed a significant negative direct effect of lifetime cocaine use on the isthmus cingulate and an indirect effect of cocaine use mediated by CTQ score. Our findings suggest that a history of ELS could aggravate the negative effects of chronic cocaine use on the cingulate gyrus, particularly in the right isthmus cingulate cortex.

Exploring the Role of DARPP-32 in Addiction: A Review of the Current Limitations of Addiction Treatment Pathways and the Role of DARPP-32 to Improve Them.

We are amidst a global addiction crisis, yet stigmas surrounding addiction counterintuitively prevail. Understanding and appreciating the neurobiology of addiction is essential to dissolve this stigma and for the development of new pharmacological agents to improve upon currently narrow therapeutic options. This review highlights this and evaluates dopamine-and-cAMP-regulated phosphoprotein, Mr 32 kDa (DARPP-32) as a potential target to treat various forms of substance abuse. Despite the proven involvement of DARPP-32 in addiction pathophysiology, no robust investigations into compounds that could pharmacologically modulate it have been carried out. Agents capable of altering DARPP-32 signalling in this way could prevent or reverse drug abuse and improve upon currently substandard treatment options.

Development and implementation of a virtual interprofessional escape room to reinforce tobacco cessation concepts

It is vital that healthcare professionals work together in a concentrated effort to help patients achieve tobacco cessation. As such, it is essential that students in health professions programs learn the Interprofessional Education Collaborative (IPEC) core competencies of collaborative practice including communication, teamwork , values and ethics, and professional roles and responsibilities to be effective members of patient care teams. This article describes the development and implementation of an interactive, virtual escape room instructional activity that reinforced important tobacco cessation concepts with pharmacy, dental, dental hygiene and physician assistant students . Interprofessional groups consisted of 6–7 students, and students were given 60 min to work through thirteen escape room puzzles to solve two patient cases related to tobacco cessation and to successfully escape. Puzzle concepts included pharmacology, contraindications and dosing of medications, drug-drug interactions, behavioral modifications, health risks associated with tobacco use, motivational interviewing, risks of vaping, vaccines and neurobiology of addiction. One hundred and thirty-five students participated in the interprofessional activity, and students completed pre- and post-surveys to assess knowledge gains and perceptions of the virtual escape room. Students reported an improvement in four interprofessional competencies of collaborative practice, and knowledge improved on all twelve conceptual questions, with seven questions showing statistically significant improvements. Student perceptions of the escape room were overall positive, with 84% of students reporting that they will use knowledge that they gained from the escape room in their professional practice. In conclusion, the use of this educational instructional activity was an effective way to reinforce and emphasize important tobacco cessation concepts and to promote the core competencies of interprofessional education and practice. Allowing students to work together and recognize the contributions of different members of the healthcare team has vital implications for helping patients achieve tobacco cessation, which has the potential to improve patient health, reduce healthcare costs and prevent both acute and chronic diseases.

An extended amygdala-midbrain circuit controlling cocaine withdrawal-induced anxiety and reinstatement.

SUMMARYAlthough midbrain dopamine (DA) circuits are central to motivated behaviors, our knowledge of how experience modifies these circuits to facilitate subsequent behavioral adaptations is limited. Here we demonstrate the selective role of a ventral tegmental area DA projection to the amygdala (VTADA→amygdala) for cocaine-induced anxiety but not cocaine reward or sensitization. Our rabies virus-mediated circuit mapping approach reveals a persistent elevation in spontaneous and task-related activity of inhibitory GABAergic cells from the bed nucleus of the stria terminalis (BNST) and downstream VTADA→amygdala cells that can be detected even after a single cocaine exposure. Activity in BNSTGABA→midbrain cells is related to cocaine-induced anxiety but not reward or sensitization, and silencing this projection prevents development of anxiety during protracted withdrawal after cocaine administration. Finally, we observe that VTADA→amygdala cells are strongly activated after a challenge exposure to cocaine and that activity in these cells is necessary and sufficient for reinstatement of cocaine place preference.

Saliva RNA Biomarkers of Gastrointestinal Dysfunction in Children With Autism and Neurodevelopmental Disorders: Potential Implications for Precision Medicine.

Gastrointestinal (GI) disorders are common in children with neurodevelopmental disorders such as autism spectrum disorder (ASD). A limited understanding of the biologic factors that predispose this population to GI disorders has prevented development of individualized therapies to address this important medical issue. The goal of the current study was to determine if elements of the salivary micro-transcriptome could provide insight into the biologic perturbations unique to children with ASD-related GI disturbance. This cohort study included 898 children (ages 18–73 months) with ASD, non-ASD developmental delay (DD), or typical development (TD). The saliva micro-transcriptome of each child was assessed with RNA-seq. Outputs were aligned to microbial and human databases. A Kruskal Wallis analysis of variance (ANOVA) was used to compare levels of 1821 micro-transcriptome features across neurodevelopmental status (ASD, DD, or TD) and GI presence or absence. An ANOVA was also used to compare micro-transcriptome levels among GI sub-groups (constipation, reflux, food intolerance, other GI condition, no GI condition), and to identify RNAs that differed among children taking three common GI medications (probiotics, reflux medication, or laxatives). Relationships between features identified in ANOVA testing were examined for associations with scores on the Autism Diagnostic Observation Schedule, 2nd Edition (ADOS-2) and the Vineland Adaptive Behavior Scales. GI disturbance rates were higher among children with ASD than peers with TD but were similar to those with DD. Five piwi-interacting RNAs and three microbial RNAs displayed an interaction between developmental status and GI disturbance. Fifty-seven salivary RNAs differed between GI sub-groups–with microRNA differences between food intolerance and reflux groups being most common. Twelve microRNAs displayed an effect of GI disturbance and showed association with GI medication uses and measures of behavior. These 12 microRNAs displayed enrichment for 13 physiologic pathways, including metabolism/digestion long-term depression, and neurobiology of addiction. This study identifies salivary micro-transcriptome features with differential expression among children with ASD-related GI disturbance. A subset of the RNAs displays relationships with treatment modality and are associated with autistic behaviors. The pathobiologic targets of the micro-transcriptome markers may serve as targets for individualized therapeutic interventions aimed at easing pain and behavioral difficulties seen in ASD-related GI disturbance.

Contingent stimulus delivery assay for zebrafish reveals a role for CCSER1 in alcohol preference.

Alcohol use disorders are complex, multifactorial phenomena with a large footprint within the global burden of diseases. Here, we report the development of an accessible, two-choice self-administration zebrafish assay (SAZA) to study the neurobiology of addiction. Using this assay, we first demonstrated that, although zebrafish avoid higher concentrations of alcohol, they are attracted to low concentrations. Pre-exposure to alcohol did not change this relative preference, but acute exposure to an alcohol deterrent approved for human use decreased alcohol self-administration. A pigment mutant used in whole-brain imaging studies displayed a similar relative alcohol preference profile; however, mutants in CCSER1, a gene associated with alcohol dependence in human genetic studies, showed a reversal in relative preference. The presence of a biphasic response (hormesis) in zebrafish validated a key aspect of vertebrate responses to alcohol. SAZA adds a new dimension for discovering novel alcohol deterrents and studying the neurogenetics of addiction using the zebrafish.

An operant ethanol self-administration paradigm that discriminates between appetitive and consummatory behaviors reveals distinct behavioral phenotypes in commonly used rat strains

Alcohol use disorder (AUD) constitutes a major burden to global health. Recently, the translational success of animal models of AUD has come under increased scrutiny. Efforts to refine models to gain a more precise understanding of the neurobiology of addiction are warranted. Appetitive responding for ethanol (seeking) and its consumption (taking) are governed by distinct neurobiological mechanisms. However, consumption is often inferred from appetitive responding in operant ethanol self-administration paradigms, preventing identification of distinct experimental effects on seeking and taking. In the present study, male Long-Evans, Wistar, and Sprague-Dawley rats were trained to lever press for ethanol using a lickometer-equipped system that precisely measures both appetitive and consummatory behavior. Three distinct operant phenotypes emerged during training: 1) Drinkers, who lever press and consume ethanol; 2) Responders, who lever press but consume little to no ethanol; and 3) Non-responders, who do not lever press. While the prevalence of each phenotype differed across strains, appetitive and consummatory behavior was similar across strains within each phenotype. Appetitive and consummatory behaviors were significantly correlated in Drinkers, but not Responders. Analysis of drinking microstructure showed that greater consumption in Drinkers relative to Responders is due to increased incentive for ethanol rather than increased palatability. Importantly, withdrawal from chronic ethanol exposure resulted in a significant increase in appetitive responding in both Drinkers and Responders, but only Drinkers exhibited a concomitant increase in ethanol consumption. Together, these data reveal important strain differences in appetitive and consummatory responding for ethanol and uncover the presence of distinct operant phenotypes.

Sugars and Sweet Taste: Addictive or Rewarding?

The notion of food “addiction” often focuses on the overconsumption of sweet tasting foods or so-called sugar “addiction”. In the extreme, some have suggested that sugar and sweet tastes elicit neural and behavioral responses analogous to those observed with drugs of abuse. These concepts are complicated by the decades long uncertainty surrounding the validity and reproducibility of functional magnetic resonance imaging (fMRI) methodologies used to characterize neurobiological pathways related to sugar and sweet taste stimuli. There are also questions of whether sweet taste or post-ingestion metabolic consequences of sugar intake would lead to addiction or excessive caloric intake. Here, we present a focused narrative review of literature related to the reward value of sweet taste which suggests that reward value can be confounded with the construct of “addictive potential”. Our review seeks to clarify some key distinctions between these constructs and questions the applicability of the addiction construct to human over-eating behaviors. To adequately frame this broad discussion requires the flexibility offered by the narrative review paradigm. We present selected literature on: techniques used to link sugar and sweet tastes to addiction neurobiology and behaviors; sugar and sweet taste “addiction”; the relationship of low calorie sweetener (LCS) intake to addictive behaviors and total calorie intake. Finally, we examined the reward value of sweet tastes and contrasted that with the literature describing addiction. The lack of reproducibility of fMRI data remains problematic for attributing a common neurobiological pathway activation of drugs and foods as conclusive evidence for sugar or sweet taste “addiction”. Moreover, the complicated hedonics of sweet taste and reward value are suggested by validated population-level data which demonstrate that the consumption of sweet taste in the absence of calories does not increase total caloric intake. We believe the neurobiologies of reward value and addiction to be distinct and disagree with application of the addiction model to sweet food overconsumption. Most hypotheses of sugar “addiction” attribute the hedonics of sweet foods as the equivalent of “addiction”. Further, when addictive behaviors and biology are critically examined in totality, they contrast dramatically from those associated with the desire for sweet taste. Finally, the evidence is strong that responses to the palatability of sweets rather than their metabolic consequences are the salient features for reward value. Thus, given the complexity of the controls of food intake in humans, we question the usefulness of the “addiction” model in dissecting the causes and effects of sweet food over-consumption.

Application of optogenetics and in vivo imaging approaches for elucidating the neurobiology of addiction.

The neurobiology of addiction has been an intense topic of investigation for more than 50 years. Over this time, technological innovation in methods for studying brain function rapidly progressed, leading to increasingly sophisticated experimental approaches. To understand how specific brain regions, cell types, and circuits are affected by drugs of abuse and drive behaviors characteristic of addiction, it is necessary both to observe and manipulate neural activity in addiction-related behavioral paradigms. In pursuit of this goal, there have been several key technological advancements in in vivo imaging and neural circuit modulation in recent years, which have shed light on the cellular and circuit mechanisms of addiction. Here we discuss some of these key technologies, including circuit modulation with optogenetics, in vivo imaging with miniaturized single-photon microscopy (miniscope) and fiber photometry, and how the application of these technologies has garnered novel insights into the neurobiology of addiction.

Mindfulness-Based Intervention Effects on Substance Use and Relapse Among Women in Residential Treatment: A Randomized Controlled Trial With 8.5-Month Follow-Up Period From the Moment-by-Moment in Women's Recovery Project.

We tested the efficacy of Moment-by-Moment in Women's Recovery (MMWR), a mindfulness training program adapted for ethnoculturally diverse women with complex social and clinical histories in residential treatment for substance use disorder, on substance use and relapse outcomes. Participants were randomized to MMWR (n = 100; 60% Hispanic/Latina, 18% non-Hispanic Black) or the attention control condition, Neurobiology of Addiction (n = 100; 56% Hispanic/Latina, 21% non-Hispanic Black). Substance use outcomes (days until first use, days of use, and relapse status: abstained, lapsed, relapsed) were obtained from interviewer-assisted timeline followback for an 8.5-month follow-up period spanning the intervention start through the 6-week intervention period and 7 months after the intervention ended. An intent-to-treat survival analyses showed that time delay to first marijuana use favored MMWR (hazard ratio = 0.44, 95% confidence interval = 0.20-0.98, p = .049) with a medium-to-large effect size. In negative binomial hurdle models, the MMWR group showed fewer days of marijuana use at 3.5 months (B = -1.71, SE = 0.79, incidence rate ratio = 0.18, p = .030) and a trend at 7 months after the intervention (B = -0.90, standard error = 0.55, incidence rate ratio = 0.41, p = .10). For marijuana, mindfulness practice time during the intervention predicted time delay to first use (B = 0.28, p = .006) and total abstinence days (B = 0.34, p = .002) across the 7 months after MMWR. No other substance use outcomes showed differential response to MMWR relative to controls. Only in MMWR, number of study intervention sessions attended (dose) correlated with a greater length of time to alcohol intoxication (r = .48, p < .001), fewer days of alcohol intoxication (r = -.24, p = .020), and greater improvement in mindfulness skills (r = .61, p < .01). MMWR added to an ongoing intensive residential treatment program serving vulnerable women is protective against marijuana use but no other substance use outcomes. Mindfulness practice time predicted a delay in time to first marijuana use. MMWR class attendance, an indicator of intervention dose, appears protective of alcohol intoxication at follow-up; thus, extended MMWR exposure might be useful.

Genetic variation in alcoholism and opioid addiction susceptibility and treatment: a pharmacogenomic approach

&lt;abstract&gt; &lt;p&gt;Alcohol and opioid abuse have pervasive and detrimental consequences from the individual to societal level. The extent of genetic contribution to alcoholism has been studied for decades, yielding speculative and often inconsistent results since the previous discovery of two pharmacokinetic variants strongly protective against alcoholism. The neurobiology of addiction involves innumerate genes with combinatorial and epistatic interactions, creating a difficult landscape for concrete conclusions. In contrast, pharmacogenomic variation in the treatment of alcoholism yields more immediate clinical utility, while also emphasizing pathways crucial to the progression of addiction. An improved understanding of genetic predisposition to alcohol abuse has inherent significance for opioid addiction and treatment, as the two drugs induce the same reward pathway. This review outlines current knowledge, treatments, and research regarding genetic predisposition to alcoholism, focusing on pharmacodynamic variation within the dopaminergic system and shared implications for opioid abuse. Multifaceted and highly polygenic, the phenotype of addiction seems to grow more complex as new research extends the scope of its impact on the brain, body, and progeny.&lt;/p&gt; &lt;/abstract&gt;