P346_Neurobiology_of_Addiction_notes

What is Addiction?

• Addiction is a chronically relapsing brain disorder characterized by:

  • Compulsive seeking and taking of drugs

  • Loss of control in limiting intake

  • Emergence of a negative emotional state when access is prevented

Substance Use Disorders (SUD)

• Classification (DSM-5):

  • Mild (2-3 criteria met)

  • Moderate (4-5)

  • Severe (≥ 6)

• Criteria include:

  • Tolerance: requiring more of the substance for same effect.

  • Withdrawal: negative symptoms when not using the substance.

  • Unsuccessful efforts to control use.

  • Substance taken in larger amounts or over longer periods than intended.

  • Significant time spent seeking substance.

  • Continued use despite negative impacts on social, occupational, or recreational activities.

  • Recurrent use in hazardous situations.

  • Cravings or strong desire to use.

Most Popular Drugs in the US

• Overview of overdose deaths by drug and demographics (1999-2022):

  • Alcohol use (48%)

  • Binge drinking (21.7%)

  • Tobacco (21.2%)

  • Marijuana (13.4%)

  • Opioid abuse (3.3%)

  • Cocaine (1.7%), Methamphetamines (1.0%), Heroin (0.3%)

Theories of Addiction

• Opponent-Process Theory

  • Proposed by Solomon and Corbit (1974)

  • Involves two opposing processes:

    • A-process: immediate pleasurable response to drug use.

    • B-process: delayed negative withdrawal responses.

• Over repeated exposures, the intensity and duration of the B-process increase.

Incentive Sensitization

• The theory by Robinson & Berridge (1993) states:

  • Repeated exposure increases craving for a drug without increasing pleasure from it.

  • Users become sensitized to drug-related stimuli, escalating drug-seeking behaviors.

Allostasis Theory

• Developed by Koob and Le Moal (1997):

  • Integration of opponent-process theory and homeostasis

  • Consistent use leads to diminished reward and heightened anti-reward responses.

  • Continued use to alleviate negative states during abstinence.

Stages of the Addiction Cycle

• Binge/Intoxication

  • Involves the basal ganglia (VTA, NAc, striatum)

• Withdrawal/Negative Affect

  • Associated with the extended amygdala

• Preoccupation/Anticipation (Craving)

  • Involves prefrontal cortex, amygdala, and basal ganglia

Stages of the Addiction Cycle (Continued)

• Binge/Intoxication

  • Involved motivation, reward, and pathological habits.

  • Neurotransmitters: Dopamine and opioid peptides.

• Withdrawal/Negative Affect

  • Negative physical and emotional withdrawal symptoms.

  • Stress system sensitization.

  • Neurotransmitters: CRF, norepinephrine, dynorphin.

• Preoccupation/Anticipation

  • Impaired executive functions.

  • Drug-seeking stimulated by cues.

Role of Anterior Insula

• Important for awareness of body states (interoception).

• Damage to the insula allows individuals to stop substance use more easily.

• Acts as a biomarker for potential relapse during craving.

Dopamine and Reward

• Explore the reward pathways stimulated by drug intake.

• Investigate how the rate of drug absorption affects the perceived high.

Mechanisms of Action: Stimulants

• Nicotine

  • Increases brain activity, leading to higher mental alertness.

  • Withdrawal symptoms include irritability and headaches.

Mechanisms of Action: Caffeine and Cocaine

• Caffeine

  • Increases wakefulness and alertness, acting as an antagonist at adenosine receptors.

• Cocaine

  • Produces euphoria by acting on dopamine transporters, leading to overflow of dopamine in synaptic clefts.

Mechanisms of Action: Alcohol and Opioids

• Alcohol

  • Acts as a Positive Allosteric Modulator on GABA receptors, leading to sedation.

• Opioids

  • Mimic natural endorphins to relieve pain and produce euphoria.

Molecular Adaptations with Substance Use

• Chronic administration leads to changes in neural activity:

  • Increased responses to excitatory inputs.

  • Changes in receptor expression affecting dopamine levels and responses.

Summary of Molecular Changes

• Neuroadaptations result in decreased responses to natural rewards and increased responses to drugs.

• Increased Δ FosB and receptor changes lead to dysregulation within the reward pathways.