Week 5.2 Biological and Psychosocial Factors in Addictions: Brain Systems and Neurobiological Changes

Introduction and Lecturer Background

• The course is Form $3.101$: Biological and Psychosocial Factors in Addictions. This specific lecture focuses on biological changes in addiction and the brain systems involved in addictive behaviors.

• The lecturer is Femke Bijsdemont Belmont, an Associate Professor and Academic Director at the University of Melbourne. She formerly worked at the University of Adelaide, where she contributed to the development of addiction-related courses and subjects.

• As a neuroscientist, her primary interest lies in understanding individual differences in susceptibility to addiction, specifically looking at how biological differences interact with psychological or environmental factors.

• A central observation in addiction science is that while initial adaptations to drug use vary depending on the specific substance used (e.g., stimulants versus depressants), long-term addiction is characterized by a shared set of behaviors and neurobiological changes after years of use.

Objectives of the Lecture

• Explain why addiction is comprehensive and involves more than just simple adaptations to immediate drug effects.

• Identify the specific regulatory systems and brain regions that undergo structural and functional changes during the progression of addiction.

• Demonstrate how the biological adaptations described support the maintenance of continued and compulsive drug use.

• Examine two primary theoretical frameworks: the Opponent Process theory and the Incentive Sensitization process.

Core Behaviors Sustaining Drug Taking

• Addiction is maintained by a cluster of key behaviors that emerge as drug use continues:

  • Drug seeking: Actively pursuing the substance.

  • Craving: An intense, often overwhelming desire for the drug.

  • Loss of control: Inability to regulate how much or how often the drug is consumed.

  • Ignoring consequences: Continued use despite significant negative impacts on health, social life, and safety.

• These behaviors are driven by changes across the entire body and specifically within the brain, impacting the likelihood of repeated use even in the face of adverse effects.

Key Brain Regions and Structures in Addiction

• Addiction is multifaceted and involves brain areas far beyond those purely responsible for pleasure or basic drives. Key structures include:

  • Nucleus Accumbens and Central Nucleus of the Amygdala: These forebrain structures are critical for the rewarding effects of drugs. They drive the "binge-intoxication" state, where users escalate the amount and frequency of use. These areas primarily utilize reward neurotransmitters such as dopamine and opioids.

  • The Extended Amygdala: This composite structure includes the central nucleus of the amygdala, the bed nucleus of the stria terminalis ($BNST$), and the transition zone in the medial part of the nucleus accumbens. This region is vital for brain stress neurotransmitters. It is involved in the "anti-reward" effects of drug dependence—the negative feelings that drive users to consume drugs to avoid discomfort rather than to seek pleasure.

  • Medial Prefrontal Cortex ($mPFC$): This serves as the neurobiological substrate for executive functioning, which encompasses decision-making and planning. In addiction, this area is compromised, leading to a shift from conscious decision-making to impulsive and habitual behavior.

Major Neurotransmitter Systems

• Dopamine and Opioids: Key neurotransmitters involved in the reward and pleasure aspects of drug use, primarily acting in the nucleus accumbens and ventral tegmental area ($VTA$).

• Brain Stress Neurotransmitters: Specifically Corticotrophin Releasing Factor ($CRF$). This impacts hormonal, sympathetic, and behavioral responses to stressors. It mediates the negative emotional states associated with dependence.

• Glutamate: A major excitatory neurotransmitter system that plays a significant role in the nucleus accumbens and amygdala, influencing the drive to use drugs.

• Molecular Transcription Factors: Specifically $Delta\,phosB$, which is involved in long-term molecular changes that occur in the brain at the cellular level.

The Addiction Cycle and George Koop’s Model

• Research by George Koop suggests that addiction is a complex cycle where different brain regions dominate different stages of the behavior:

  • Initial Stage (Reinforcement): Use is driven by pleasurable effects (positive reinforcement). The Ventral Tegmental Area ($VTA$) is highly active here.

  • Habit Formation: Over time, the behavior moves from a choice to a habit, involving the thalamus and other regions, signaling a loss of control.

  • Withdrawal and Negative Affect: As use becomes chronic, a strong sense of withdrawal occurs when the drug is absent. The brainstem and other areas are critical in mediating this negative state.

  • Anticipation and Craving: Users begin to anticipate withdrawal and experience cue-induced cravings. If a person walks past a familiar bar or environment, the hippocampus (responsible for memory) and the amygdala (which adds emotional weight to memories) trigger an intense drive to use.

• This cycle creates a loop where the brain’s healthy functioning is effectively "hijacked" by the drug.

Opponent Process Theory

• This theory posits that drugs provoke both positive and negative feelings.

• Non-Dependent Brain: Initially, positive reinforcing effects (the "A-process") predominate. Circuits in the $VTA$ and nucleus accumbens are highly active. Negative reinforcement (the "B-process") is present (e.g., a hangover) but remains minor.

• Dependent Brain: With repeated use, a shift occurs. The brain experiences a loss of function in reward neurotransmitters and a gain of function in stress systems (like $CRF$). The positive effects diminish (tolerance), while the negative reinforcing effects (anti-reward) become very strong.

• Conclusion: Individuals start using because they like the drug, but continue using because they need to escape the negative feelings of withdrawal.

Incentive Sensitization Model

• This theory focuses on the distinction between "liking" and "wanting" a drug.

• Liking (Hedonic response): The pleasurable feelings of drug use actually decrease with repeated use.

• Wanting (Incentive salience): The craving, needing, and reaction to cues increase significantly.

• Neurobiological Basis: This model suggests a gain in function of the mesolimbic dopamine system and glutamatergic efferents to the ventral striatum. It emphasizes that addiction is driven by a sensitized drive to seek the drug rather than the pleasure derived from it.

Cognitive and Executive Functioning Impairments

• Addiction results in significant changes in how individuals process rewards and make decisions:

  • Temporal Discounting: People with addiction often value short-term gain over long-term gain. For example, in gambling tasks, individuals may value $100$ in one minute more than $1,000$ in three minutes.

  • Underestimation of Alternative Rewards: Addicted brains often fail to value non-drug activities (e.g., spending time with non-using friends, maintaining a house, or holding a job). Use becomes the primary source of reinforcement.

  • Memory Challenges: Drugs may be used as a coping mechanism to suppress bad memories, while "good" memories of prior drug use act as powerful triggers for relapse.

  • Impulsivity vs. Breaking: In a healthy brain, the prefrontal cortex acts as a "brake" on the amygdala’s impulsive drives. In an addicted brain, this brake is weakened. This is especially risky in young people, as the prefrontal cortex does not fully develop until roughly age $25$.

Recommended Resources and Discussion

• Textbooks: Principles of Addiction Medicine provides current information on how complex systems (immune, hormonal, and neurotransmission) interact in addiction.

• Interactive Tools: The University of Utah has developed educational games to help students understand how different drugs work and how addiction develops.

• External Courses: The edX platform offers a free course titled "Managing Addiction," developed by the University of Adelaide pharmacology department, which covers treatment, realistic goals for recovery, and health management.

• Contact Information: Students may email Femke Bijsdemont Belmont with questions, though they are advised to do so after the lecture rather than immediately before exams.