Biopsychological Aspects of Drug Addiction

The Nucleus Accumbens and Brain Regions

We will delve into the intricate biopsychological aspects of drug addiction, focusing on the brain regions involved and the models that shape our current understanding. Our learning outcomes include describing the role of the nucleus accumbens and related brain regions in the transition from initial to habitual to addictive drug-taking, and understanding key developments in biopsychological models of addiction.

Addiction Cycle

While habitual drug users may not necessarily be addicts, addictive drug use typically involves a habitual component. We will explore the processes that lead from initial drug exposure to habitual use and, ultimately, to craving and relapse, which characterize addictive patterns.

Three Stages of Addiction Cycle

The preeminent current model, developed by Nora Volko and George Ku, posits three stages:

1. Binge and Intoxication:
   • Driven by the reinforcing effects of the drug, engaging reward-related neurotransmitters.
   • Key brain area: nucleus accumbens in the ventral striatum.
   • Involves positive incentive, hedonic aspects of drug taking.
   • Related to incentive sensitization theory.
2. Withdrawal:
   • The extended amygdala plays a significant role.
   • Also involves the orbitofrontal cortex and locus coeruleus.
   • Withdrawal states vary across different drugs.
3. Preoccupation/Craving:
   • Relies on conditioned reinforcement.
   • Craving involves "I want it" and "I need it."
   • Inhibition is controlled by the prefrontal cortex.
   • Involves incentive sensitization theory and prefrontal cortex/regulatory control models.

Iterative experiences through intoxication, withdrawal, and craving promote addictive tendencies.

Brain Structures

Three related networks underscore the dopamine model of addiction:

1. Mesolimbic Pathway:
   • Dopamine tracts arise from the ventral tegmental area (VTA).
   • Involved in goal-oriented behaviors.
   • Increases stimulus salience, making drug cues desired incentives.
2. Nigrostriatal Pathway:
   • Arises from dopamine neurons in the substantia nigra and projects to the dorsal striatum.
   • Critical for translating reward signals into habits.
   • Dorsal striatum: habits.
   • Ventral striatum (nucleus accumbens): rewards/goal-oriented behaviors.
3. Mesocortical Pathway:
   • Connects prefrontal cortex with parts of the striatum.
   • Involved in cognitive aspects: working memory, logical reasoning.
   • Affects impulsivity, compulsivity, and reward-related processing.

Dopamine originates from the VTA, goes to the nucleus accumbens, and proliferates to the mesocortical and mesolimbic structures.

Historic Influences

Understanding addiction has evolved through different theories over time:

• 1950s: Physical Dependence Theories
  • People take drugs to offset withdrawal.
• 1960s-1970s: Positive Incentive Model
  • People take drugs because they like it.
  • Led to dopamine and intracranial models of addiction.
  • Mesocorticolimbic pathway mechanisms.
• Incentive Sensitization Theory
  • Wanting can increase more than liking.
• Prefrontal Cortex/Regulatory Control

Currently, we reconcile different lines of research across time.

Cycle of Drug Taking

Repeated binge intoxication, withdrawal/negative affect, and craving/preoccupation contribute to addiction:

Physical Dependence Model

A vicious cycle of drug taking and physical dependence maintains drug use and promotes addiction.

• People take drugs to offset withdrawal.

Caveats and Challenges:

• High relapse rates even after withdrawal/detoxification.
• Many addictive drugs (e.g., amphetamines) don't have severe withdrawal states.

Led to a shift toward positive incentive theories.

Positive Incentive Theories

Focus on the positive effects or hedonic features of drug use rather than just avoiding withdrawal.

• VTA is an early dopamine hub, projecting to the nucleus accumbens.
• Mesolimbic pathway originates from the VTA to the nucleus accumbens, driving reward-related behavior.
• Addictive substances stimulate VTA dopamine neurons, boosting dopamine in the nucleus accumbens.
• Mesocortical pathway extends from the VTA to the cerebral cortex, influencing frontal lobe functions.

The mesocorticolimbic pathway determines the functioning of brain reward systems in addiction.

Research

Olds and Milner (1954) found that rats self-stimulated particular brain areas with electricity.

• Implants connected to reward hubs in the brain.
• Intracranial self-stimulation associated with increased dopamine release.
• Dopamine agonists increase self-stimulation, while dopamine antagonists decrease it.

Rodent studies using conditioned place preference further explored specific sites in the mesocorticolimbic pathway.

• Nucleus accumbens identified as having a crucial role.
• Dopamine pathways from VTA to nucleus accumbens are reward and pleasure pathways.
• Lesions to these areas blocked conditioned place preference.

Shortcomings of Research:

• Do lab conditions reflect human conditions?
• Focus mainly on stimulants.
• Humans continue to use drugs even when it's not pleasurable.
• Cue exposure led rats to overcome aversive situations to obtain cocaine, but not sucrose.

Incentive Sensitization Theory

The incentive to get a drug is reinforced with repeated use, especially in vulnerable individuals.

• Heightened wanting/craving even though the drug may not be pleasurable.
• Dissociation between wanting versus liking.
• Different circuitry motivates wanting versus liking.
  • Wanting: nucleus accumbens and related circuits.
  • Liking: more vague and diffuse.

The urge intensity depends on the cue's reward, the person's association with a cue, and the current state of the individual.

• Amplified by stress, emotional excitement, intoxication.

Example:

• Amphetamine microinjection into the nucleus accumbens enabled specific cue pairings.
• Pavlovian reward cues trigger use.
• Maintaining cue pairing even when drug-free reinforces brain reward circuits.

Prefrontal Cortex Models of Addiction

Impaired Regulatory Control:

• Top-down regulation needed to overcome bottom-up impulsive/compulsive drug-seeking states.
• Involves mesolimbic/mesocorticolimbic reward systems.
• Prefrontal cortex acts as a braking mechanism.
• Chronic exposure to addictive drugs linked to abnormalities in the frontostriatal circuitry.
• Impairments in executive functioning, inhibition, and decision-making.

Neuropsychological evidence shows increased orbitofrontal activation in cocaine users, reduced glucose metabolism in the prefrontal areas, and lower striatal receptor binding during withdrawal.

Conclusion

Neurobiological models of addiction are complex and constantly evolving.

• Involve interconnected brain regions such as VTA, nucleus accumbens, prefrontal cortex, and amygdala.
• Each region has a different range of functions across the stages of bingeing, withdrawal, and cravings.
• Models are advanced by animal and human studies.