The Brain Story Certification: Module 13 – The Gallup Social Work Blog

Module 13: Addiction & the Brain, Part A – A
Neurobiological Perspective

U.S. Department of Health and Human Services (HHS), Office of the Surgeon General. Facing Addiction in
America: The Surgeon General’s Report on Alcohol, Drugs, and Health. Washington, DC: HHS, November
2016. https://addiction.surgeongeneral.gov/sites/default/files/surgeon-generals-report.pdf

Multiple factors contribute to addiction
Neuro biology is impacted by the environment and repetition of substance use, especially in adolescence.

Excerpt from “Neurobiology of Reward & Addiction”
Mark Gold, MD
University of Florida

Key structures for addiction
- Caudate nucleus
- Nucleus accumbens
- VTA (ventral midbrain) – dopaminergic projections to nucleus acumens, amygdala, and prefrontal cortex.
- Amygdala
- Hippocampus
- Orbitofrontal cortex
Different pathways being operated on (synergistic effects) can promote substance use.
Many different substances have increasingly become more used in the general population.

Excerpt from “The Relationship Between the Reward & Stress Systems and How They Are Perturbed
in Addiction”
George Koob, PhD
National Institute on Alcohol Abuse and Alcoholism

Accession is an incentive salience disorder, reward deficit disorder, stress surfeit disorder, and self-regulation disorder.
Chronically relapsing disorder to take a stimulus and loss of control to control limiting intake. It includes the emergence of a negative emotional state when access to the stimulus is removed.
Impulse control disorder – positive-reinforcement driven. Thrill-seeking to the extreme
Compulsive disorder – more harm/anxiety-driven.
The addiction cycle is a combination of impulse control disorder and compulsive disorder.
Driving forces are positive and negative reinforcement.
Positive reinforcement – presentation of the stimulus increases the probability of a response.
Negative reinforcement – removal of an adverse stimulus increases the probability of a response. Alleviates the pain. This is a primary force in the beginning use of a substance.
Cycles of prevalent in process addictions (non-chemical). The pattern is common to all compulsive disorders.
There may be common elements between process and substance addictions.
Neurobiology of addiction – Prefrontal cortex, dorsal striatum, Nucleus accumbens, orbitofrontal cortex, thalamus, globus pallidus, hippocampus, insula, amygdala, and bed ucleus of the stria terminals.
Withdrawal/negative affect takes place in the amygdala and the nucleus of the stria terminals.
Binge/intoxication takes place in the thalamus, globus pallidus, nucleus accumbens, and dorsal striatum.
Preoccupation/Anticipation takes place in the prefrontal cortex, orbitofrontal cortex, hippocampus, and insula.
The reptilian brain plays a role in addiction.

Excerpt from “The Relationship Between the Reward & Stress Systems and How They Are Perturbed
in Addiction”
George Koob, PhD
National Institute on Alcohol Abuse and Alcoholism

Binge-Intoxication Stage
- dopamine is a key component. Cocaine blocks reuptake. Methamphetamine blocks reuptake and reverses transport – dopamine dump.
- Mesolimbic dopamine system – VTA & NA
  - Rewarding component
- Drugs overwhelm a system that orients us towards what is important in the environment.
- The dopamine system is critical to the self-administration of substances (especially cocaine).
- Alcohol does release some dopamine but releases endorphins (opiod-peptides) – triggering nucleus accumbens along another pathway.
- Nucleus accumbens has a high concentration of opioid receptors.
- Opioid receptors are critical for the reinforcing effects of alcohol.
- Incentive salience
  - drug-seeking taking habits
  - compulsive drug-seeking
  - abstinence/relapse
  - vulnerability
  - goal-directed drug-seeking/taking Pavlovian conditioning
- Substance use becomes a habit.

Excerpt from “The Relationship Between the Reward & Stress Systems and How They Are Perturbed
in Addiction”
George Koob, PhD
National Institute on Alcohol Abuse and Alcoholism

Withdrawal-negative affect
- gain stress system at the loss of the reward system
- Opponent process: what goes up must come down – addiction gets rid of the non-depressant component, leaving the depressant process. Examples include dopamine dysphoria, opioid peptides for pain, serotonin dysphoria, less GABA that influences anxiety and panic attacks. Dopamine receptors decrease – there is plasticity in receptors (up/downregulation of receptors).
- Corticotropin-Releasing Factor – the conductor of the body-stress response (HPA-axis). All substances of abuse activate the CRF system – particularly alcohol. CRF antagonists block the stress system impacts on addiction.
- Senitizing systems take place from each substance binge. Stress system – contributes to decreasing in reward function

Excerpt from “The Relationship Between the Reward & Stress Systems and How They Are Perturbed
in Addiction”
George Koob, PhD
National Institute on Alcohol Abuse and Alcoholism

Functions of the frontal cortex – a key role in craving/craving/preoccupation. IT is multi-determined by cues with the drug. Linked to the habit system. Think of Mitschel “hot system.”
The frontal cortex is the stop system (cold system). We can make decisions. This is impaired in addiction. Behavioural treatments strengthen the stop system (CBT & Mindfulness interventions may be useful here).
The ventral part of the prefrontal cortex is impacted – changing executive processing.. This perpetuates the states that allow addiction to exist.

Childhood ACEs can influence the risk factors associated with addiction. Especially the frontal cortex.
There be pre-existing vulnerabilities for some individuals – including the size of the frontal cortex.
Some genes that influence the metabolism of alcohol and nicotine have been associated with addiction. At the same time, others that affect proteins involved in mechanisms that influence the addiction cycle have also been implicated. Thus, there is a complex interplay between the person and their environment.

Excerpt from “Early Genetic & Environmental Factors Affecting the Reward & Motivation System”
Pat Levitt, PhD
University of Southern California

How exposure during early development changes the developmental trajectory – there are various neurodevelopmental consequences. The sensitive periods’ influence when the substance changes the structures.
Neurotransmitters help in organizing the brain structure. Disruption in sensitive periods of brain architecture impacts development. Guidance and growth molecules for the brain.
Neuromodulators can modulate signals going into other cells.
Impacts of prenatal cocaine on fetal development
Non-drug factors in early development can also alter the neuromodulation systems (experiences and substances can have an impact).
ACES change the structure of reward systems.
Gene-environment interactions are essential in brain development.
Where the neurotransmitter is profused to influences the growth of a region.
Long-term outcomes depend on the social-emotional issues of child development.
The systems of the brain are built over time – different systems are impacted at different times, by different substances/experiences.

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