Neurobiology of Addiction

Addiction was historically viewed as a disease of “weak personality” and was not systematically addressed by the scientific and medical communities until the latter half of the 20th century.  They are now commonly accepted as diseases of the brain caused by the impact of the drug on the brain (direct effects and neuroadaptations) modified by environmental factors.

Drug addiction can be considered a chronic brain disease that affects neurotransmission between neuronal circuits controlling behavior, emotion and cognition; characterized by excessive drug use, unsuccessful attempts in controlling drug intake leading to increase in anxiety and emotional pain. Thus, addiction results from repeated long-term exposure to drugs, leading to changes in central nervous system, especially in the midbrain dopamine system, resulting in an addictive state with complex behaviors such as dependence, tolerance, sensitization, and craving. However, addiction leading to loss of volitional control (opiates, nicotine and illicit use of psychostimulants), if left untreated, can cause major medical, social, and economic problems.

Drug addiction represents a dramatic dysregulation of motivational circuits caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress. Three phenomena characterize addiction: binge/intoxication, withdrawal/negative affect and craving (preoccupation/anticipation). Impulsivity and positive reinforcement often dominate the first stages, driving the motivation for drug seeking, and compulsivity and negative reinforcement dominate the terminal stages of the addiction cycle.

Binge/intoxication: Addictive substances and rewarding behaviors, increases the release of dopamine from mesolimbic projections to the nucleus accumbens. Thus, dopamine signals a pleasurable experience and is critical for the reinforcing effects which releases dopamine in the mesolimbic area, the corpus striatum, and the frontal cortex thereby promoting self-administration

Withdrawal/negative affect: The increase in negative emotional states in the withdrawal stage involve decrease in the dopamine function. These neuronal changes lead to dysphoric and stress-like responses. Repeated drug intake during withdrawal, results in a vicious cycle.

Craving (preoccupation/anticipation): The craving and deficits in executive function in the so-called preoccupation/anticipation stage involve the dysregulation of key afferent projections from the prefrontal cortex to the basal ganglia and extended amygdala. Impaired dopamine and glutamate signaling in the prefrontal regions weakens the ability to resist strong urges to stop taking the drug. Thus, despite the potentially catastrophic consequences, it develops compulsive behavior and the associated inability to voluntarily reduce drug- taking behavior.

Molecular genetic studies have identified transduction and transcription factors that might mediate initial vulnerability, maintenance, and relapse associated with addiction

Summary

• Addiction-relevant behaviors in animal studies model have led to an understanding of addiction neurobiology and identification of several genes mediating variation in drug preference and response

• The neurobiological pathways that modulate reward, stress resiliency and behavior inhibition are among those having underlying addiction liability.
• Variation in the neurobiology of addiction is genetically influenced by correlation of addiction liability with heritability.
• The individualization of treatment and prevention is likely to be advanced by the discovery of genetic predictors of the neurobiological pathways that underlie addiction

Tenured Professor and Director of Laboratory: WHO Collaborative National Drug Dependence Treatment Center, All India Institute of Medical Sciences…an Internationally reputed hospital and Research Institute, New Delhi, India

Educational Background

• PhD, Delhi University, India
• Post doc in Pharmacology and Clinical Pharmacology, All India Institute of Medical Sciences, New Delhi, India

Honors & Awards

• Invited to be KEYNOTE speaker at Addiction meetings/conference
• International Visiting Exchange Faculty/Scientist Award, NIDA (worked at University of Pennsylvania)        
• Distinguished International Scientist Collaborative Award (DISCA), NIDA (worked in LSUHSC, LA)        
• Chaired Scientific Sessions on “Addiction” in American Psychiatric Association (APA) Meeting from 2002-2012
• UN Fellowship Awarded for Advanced training in Addiction at University of Glasgow, Scotland, UK
• Visiting Professor, Rutgers University, Rutgers
• Visiting Professor, University of Iowa
• Fellow of Royal Society of Chemists (C.Chem, FRSC, LONDON)
• Elected on “Board of Directors” for Asia Pacific Society for Alcohol and Addiction Research (APSAAR)
• Invited by Japan to Represent India for formulating by laws of APSAAR
• Elected as Member of National Academy of Medical Sciences in India (MNAMS)
• Nominated as Honorary member of “Board of Directors” by Scientific Council of Skibbereen University, UK
• Best Paper awards
• Elected on “Research Board of Advisers” of American Biographical Institute (ABI)

Publication Summary

• Peer-reviewed research articles.
• Invited to Publish Chapters on Addiction for “Elsevier Publications”
• Invited to Publish Chapters on Addiction in “International Series of Addiction” Praeger Publications, USA.
• Invited to Publish Chapters in Advances in Psychology “Nova Science Publishers’, Inc. USA.
• Chapter in “Genomics and Health in the Developing World” Oxford Publishers
•  Chapter in Substance Use Disorder, Indian Publishers.

International Presentations in Research Society of Alcoholism (RSA), International Society of Biological Research on Alcoholism (ISBRA) and other forums:

• The importance of ALDH2 and ADH2 loci for alcohol dependence among Indian alcoholics at ISBRA/RSA joint meeting held at Washington DC
• Single nucleotide polymorphism in genes encoding for various alcohol metabolizing enzymes: correlation with alcohol induced tissue specific damage at ISBRA/RSA joint meeting held at Washington DC.
• Role of Alcohol Metabolizing genes in Alcohol induced Pancreatitis, RSA USA.

• Genetic predisposition in Alcohol Dependence: Role of DRD2 genes in Indian population: First Study RSA, USA
• HIV Sero-prevalence in a serial sample of patients at Drug Dependence Treatment Centre (DDTC) at AIIMS, New Delhi, India American Psychiatric Association meetings in New Orleans, LA, USA,
• Single nucleotide polymorphism in genes encoding for various alcohol metabolizing enzymes: correlation with alcohol induced tissue damage RSA, USA
• Alcohol Research in India, Japan Society of Psychiatric Research of Alcoholism, OTSU, Japan
• Alcohol and Depression in India ISBRA, Sydney
• Alcohol metabolizing pathway genes in alcohol dependence AND alcoholic pancreatitis ISBRA, Paris
• Neurodegenerative effects & Genetic Pathways in Alcoholism, International Symposium Singapore
• Patterns of alcohol consumption and management in India: Role of gender and culture, Melbourne
• Dopaminergic pathway genes in alcoholism, SEOUL S. Korea
• Patterns of alcohol consumption and management system in diverse (Asian) Countries: roles of gender and culture, Melbourne
• Genetics of Drug Abuse and Alcoholism on Indian Population, Invited talk, Pakistan

NIDA Oral Presentations: College on Drug Dependence (CPDD)

• Effects of the Combination of Metyrapone and Oxazepam on the Cue-Induced Reinstatement of Cocaine Seeking USA
• An overview of substance abuse in India USA
• Association study of the β-arrestin2 (ARRB2) with Opioid and Cocaine dependence in a European American Sample USA
• SNP polymorphisms in the δ-opioid receptor, OPRD1, with cocaine and opioid addicted populations, USA

NK cell activity and Infections in Non Parenteral in Heroin Dependence: A pilot study from India CPDD Meeting in Quebec, Canada.