1. The Neurobiology of Addiction
Kim Edward Light, Ph.D.
Professor, College of Pharmacy
University of Arkansas for Medical Sciences

2. Objectives Review definitions for abuse, dependance, and addiction.
Outline the brain areas involved in drug use and drug seeking including the limbic, hypothalamic, prefrontal cortex, orbitofrontal cortex, and anterior cingulate gyrus.
Delineate the meaning of reward and how neuronal pathways are involved in signaling reward.
Identify the neurotransmitter mediating the reward signal and how various behaviors and substances trigger reward neurotransmission.
Outline the current neural interconnections involved in reward neurotransmission.
Identify how motivation controls behavior and impacts drug abuse and addiction.

3. Definitions
DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, ed 4. American Psychiatric Association, Washington, 1994.
The American Society of Addiction Medicine (ASAM).
The American Academy of Pain Medicine (AAPM).
The American Pain Society (APS).

4. Alcohol or Drug Abuse
DSM-IV Definitions
one (or more) of the following, occurring within a 12-month period
recurrent substance use resulting in a failure to fulfill major role obligations at work, school, or home
recurrent substance use in situations in which it is physically hazardous
recurrent substance-related legal problems
continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance

5. Alcohol or Drug Dependence
DSM-IV Definitions
three (or more) of the following, occurring at any time in the same 12-month period:
Tolerance
Withdrawal
Relapse
A great deal of time is spent in activities necessary to obtain, use or recover from the substance
Important social, occupational, or recreational activities are given up or reduced because of substance use
Continued use despite adverse consequences

6. Addiction
The American Society of Addiction Medicine (ASAM), the American Academy of Pain Medicine (AAPM), and the American Pain Society (APS)
Addiction is a primary, chronic, neurobiological disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations.

7. Addiction Impaired control over drug use,
Characterized by:
Impaired control over drug use,
Craving and/or compulsive use,
Continued use despite harm,
Relapse.

8. Addiction Neurobiology
Animal models
Must demonstrate these behaviors
Neuronal substrates and basis can be investigated.
Slide image from NIDA

9. Reward Pathway
Intracranial self-stimulation identifies neural pathways
Reinforcement or “reward” involves
the acquisition of pleasure (positive)
the avoidance of pain (negative).
Several important brain areas

10. Limbic System Several structures contained in both hemispheres
Linkages to the hypothalamus and other portions of the mid-brain.
Concerned with feelings and emotions.
Critical to memory processing and reward
Cingulate gyrus
Amygdala
Hippocampus
Dentate Gyrus
“Reward Pathway”

11. Hypothalamic Structures
Controls hunger, thirst, reproductive drive, temperature, blood pressure
Maintains hormonal balance
Hypothalamus
Pituitary Gland
Stress Response Center

12. Prefrontal & Orbitofrontal Cortex
Cognition, Judgment, Planning, Inhibitions, Personality,
Right/wrong
Decision making

13. Why Rewards? Natural Rewards or Instinctive Behaviors promote survival
Food acquisition
Water intake
Procreation (sex)
Nurturing / protection
Activities that “feel good” are noticed and repeated

14. Brain Structures of Reward
VTA
NcA
PFC
ACG
OFC
ACG - Anterior Cingulate Gyrus
PFC - Pre-frontal cortex
OFC - Orbitofrontal cortex
NcA - Nucleus Accumbens
VTA - Ventral Tegmental Area

15. Reward Signaling Mediated by Dopamine Neurotransmission
Activity
Increase in DA release NcA
Food or sexual activity
50 – 100%
Alcohol, MJ, Nicotine
125 – 225%
Morphine, Heroin %
Cocaine
400%
Methamphetamine
1000%

16. Neurotransmitters and Reward
Glu Op
Nucleus
Accumbens
Frontal Cortex
ACG
(+)
(-)
Saliency
(+) DA
GABA
(-)
GABA
(-)
Ventral Tegmental Area
Op – opiate pathway
Glu – glutamate pathway
GABA – GABA pathway
DA – dopamine pathway
(-) Op

17. Pre-frontal Cortex Functions
Limit or reducing consumptive behavior
Inhibition of the amygdala (fear) and the stress response
Shifting attention
Balancing several inputs at once (multi-tasking)
Focusing short term memory for processing to long term

18. Orbitofrontal Cortex Function
Processing emotional behavior
Interpretation of emotional behavior
Information for planning
Linking an actions with a negative consequence

19. Anterior Cingulate Gyrus Functions
Emotion and awareness
Mediates conflict between emotional desires and intellectual values
“wanting” - and - “likely harm or wrongness”
Intellect control of emotion

20. Motivation Important process that drives human behavior
Appetitive - desire or “appetite”; commonly associated with “hedonic” or the seeking of pleasure
Aversive – avoidance of pain or unpleasant experiences

21. Motivation
Pleasure and pain are the principle aspects of motivational processes;
Arise in the Limbic areas of the brain
Meaning or interpretation provided by the PFC, OFC, ACG.
Two states of stress - Hypothalamus
Eustress (positive)
Distress (negative)

22. Addiction Neurobiology
On a neurobiological basis then addiction can be viewed as:
a disruption or dysfunction of these pathways that may involve inadequate reward signaling from the limbic areas associated with certain behaviors,
and/or
a diminished ability of the prefrontal cortex and anterior cingulate gyrus to properly formulate responses to emotional information delivered by the limbic and hypothalamic areas.

23. Intellect
Intellect
Emotional
Emotional

24. Addiction Current hypothesis
Pathology of addiction involves
inherent (genetic)
and/or
drug-induced
alterations in the ability of the PFC, OFC, ACG to process and appropriately respond to information identified as important by DA neurotransmission from the reward pathway.

25. Review Definition of abuse, dependance, and addiction.
Brain pathways that mediate and govern behaviors.
Neurobiology of reward and its interpretation
Activation of the reward pathway by drugs of abuse.
Alterations in the higher brain areas that receive the reward pathway communication.
Role of motivation in behavioral control and the hypothesized pathology of addiction.