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Kim Edward Light, Ph.D.Professor, College of PharmacyUniversity of Arkansas for Medical Sciences
The Neurobiology of Addiction
Objectives
1. Review definitions for abuse, dependance, and addiction.
2. Outline the brain areas involved in drug use and drug seeking including the limbic, hypothalamic, prefrontal cortex, orbitofrontal cortex, and anterior cingulate gyrus.
3. Delineate the meaning of reward and how neuronal pathways are involved in signaling reward.
4. Identify the neurotransmitter mediating the reward signal and how various behaviors and substances trigger reward neurotransmission.
5. Outline the current neural interconnections involved in reward neurotransmission.
6. Identify how motivation controls behavior and impacts drug abuse and addiction.
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).
Alcohol or Drug Abuse DSM-IV Definitions one (or more) of the following, occurring within a 12-
month period1. recurrent substance use resulting in a failure to fulfill
major role obligations at work, school, or home
2. recurrent substance use in situations in which it is physically hazardous
3. recurrent substance-related legal problems
4. continued substance use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of the substance
Alcohol or Drug DependenceDSM-IV Definitions
three (or more) of the following, occurring at any time in the same 12-month period:
1. Tolerance
2. Withdrawal
3. Relapse
4. A great deal of time is spent in activities necessary to obtain, use or recover from the substance
5. Important social, occupational, or recreational activities are given up or reduced because of substance use
6. Continued use despite adverse consequences
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.
Addiction
Characterized by:
1. Impaired control over drug use,
2. Craving and/or compulsive use,
3. Continued use despite harm,
4. Relapse.
Addiction Neurobiology
Animal models Must demonstrate these behaviors Neuronal substrates and basis can be
investigated.
Slide image from NIDA
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
Cingulate gyrus
Amygdala
Hippocampus
Dentate Gyrus
“Reward Pathway”
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
Hypothalamus
Pituitary Gland
Hypothalamic Structures Controls hunger, thirst, reproductive drive,
temperature, blood pressure Maintains hormonal balance
Stress Response Center
Prefrontal Orbitofrontal
Cortex
Cognition, Judgment, Planning,
Inhibitions, Personality,Right/wrong
Decision making
Prefrontal & Orbitofrontal Cortex
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
VTA
NcA
PFC
ACG
OFC
ACG - Anterior Cingulate Gyrus
PFC - Pre-frontal cortex
OFC - Orbitofrontal cortex
NcA - Nucleus Accumbens
VTA - Ventral Tegmental Area
Brain Structures of Reward
Reward Signaling Mediated by Dopamine Neurotransmission
ActivityIncrease in DA
release NcA
Food or sexual activity 50 – 100%
Alcohol, MJ, Nicotine 125 – 225%
Morphine, Heroin 150 - 300%
Cocaine 400%
Methamphetamine 1000%
Frontal Cortex
ACG
Ventral Ventral Tegmental Tegmental
AreaArea
Nucleus Nucleus AccumbensAccumbens
DADAGABA
GABA
Glu
Op
Op
Op – opiate pathwayGlu – glutamate pathwayGABA – GABA pathwayDA – dopamine pathway
(-)
(-)
(-)(-)
(+)
(+)
Saliency
Neurotransmitters and Reward
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
Orbitofrontal Cortex Function
Processing emotional behavior Interpretation of emotional behavior Information for planning Linking an actions with a negative
consequence
Emotion and awarenessMediates conflict between emotional
desires and intellectual values “wanting” - and - “likely harm or
wrongness” Intellect control of emotion
Anterior Cingulate Gyrus Functions
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
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)
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.
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.
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.