Download Review of Neurobiology

Addiction is a Brain Disease
Michael L. Johnson, MS
Nancy A. Roget, MS
Brain Disease
Drug addiction is a brain disease
 Every type of psychoactive drug
has its own individual mechanism
for changing how the brain
functions
Drug use changes the individual's
brain and its functioning in critical
ways
Leshner, 2001
Addiction is a Brain Disease
Addiction is a Brain Disease
BECAUSE:
Using drugs over time changes brain
structure and function
 Some brain changes may persist
after use stops
Long-lasting brain changes effect
 cognitive functioning
 emotional functioning
Addiction is a Brain Disease
Addiction is a brain disease
 addicted brain is different from the nonaddicted brain
Prolonged drug use causes pervasive changes
in brain function
Essence of Addiction
 Compulsive craving that
overwhelms all other
motivations (drug use despite
negative and social
consequences)
 root cause of health and social
problems
Paradox of Addiction
Initially Voluntary
Addiction’s Similarities with
Other Brain Diseases
Some brain diseases are NOT
simply biological in nature and
expression
Most have social/behavioral aspects
Examples:
Alzheimer's
Schizophrenia
 Clinical Depression
The Adult Brain,
and how it works
An Adult
brain
weighs
about 3
pounds and
has billions
of cells
Neurons
Glial cells
The Brain
Organ on thinking, behavior,
homeostasis
Different Areas of the brain regulate
different functions
Complex tasks are split up into
specialized areas
Damage to these areas leads to specific
deficits
“Division of labor” allows for Parallel
Processing
Brain Region & Function
Splits larger tasks into smaller
ones
Component tasks are further
broken into sub component
tasks
Driving
Seeing
Hearing
Moving
Understanding
How
the
Brain
Works
Understanding
How
the
Brain
Works
Function of Brain Regions
Brainstem= basic function
Heart rate, breathing, digestion, sleep
Cerebellum =skilled repetitive
movements, balance
Limbic System=emotions &
motivations
Diencephalon=sensory perception
Function of Brain Regions
Cerebral Cortex = thinking,
perceiving, producing language
Vision, hearing, touch, movement,
smell, thinking & reasoning
Frontal Lobe = social behavior Limbic
System
Uses memories, information about how
the body is working and sensory input
Function and Brain Regions
Phineas Gage
1848 Railroad
worker
Explosion- tamping
rod
Rod entered brain
Temperament
changes
20 years post
accident
Correlated accident
to behavioral
changes
Frontal lobe = social
behavior
Neurons, Brain Chemistry &
Neurotransmission
The
Neuron
Basic signaling unit of
brain
Precise connections allow
for different actions
Neurons
Sensory receptors
Muscles
The
Neuron
Cell
Body
–Nucleus
–Metabolic center
Dendrites
–Input from other
neurons
Axon
–Carry high speed
messages away
from neuron
–Branches into
presynaptic
terminals
The Synapse
The Synapse
N
E
U
R
O
T
R
A
N
S
M
I
T
T
E
R
S
The
 End of axon
 Typical neuron has 1000 synapses with other
neurons
 Intercellular space between neurons
 Synaptic cleft
S
y
n
a
p
s
e
Synapses are Dynamic
Neurons can strengthen synaptic
connections
New synapses form (protein
synthesis)
Synapses can be lost
Responses to life experiences
(and aging)
Cellular basis of learning
Synaptic Transmission
Neurons communicate via
electrical and chemical signals
Electrical signal converted to a
chemical signal– a
neurotransmitter
Electrical signal within a
neuron is an action potential
Wave-like flow of ions (electrical
impulse) down axon
Transient depolarization of axon
Synaptic Transmission
At the axon
terminal, the
electrical impulse
leads to release of a
neurotransmitter
Stored in vesicles
which fuse with the
neuronal membrane
and release their
contents into the
cleft
Synaptic Transmission
 Neurotransmitters
diffuse into
intercellular space
 Bind to receptors on
dendrite of another
cell
Postsynaptic cell
Receptors are
specific
Dopamine receptors
will only bind
dopamine
Synaptic Transmission
Chemical binding
of transmitter
with receptor
leads to changes
in the postsynaptic cell
May generate an
action potential
Post-synaptic cell
may use a
different
neurotransmitter
to communicate
“down stream”
Neurotransmission
Synaptic Transmission
 After binding,
neurotransmitters
releases from receptor
and goes back into the
cleft
 Removed by enzymes
or reuptake pump/
transporter back into
terminal
 quick removal of
transmitters allow for
precise communication
between neurons
Types of Neurotransmitters
A neuron receives many many
messages from connecting neurons
Neuron’s response is the “sum”
Excitatory Transmitters
Lead to (generation of A’s and) stimulate
firing of post-synaptic neuron
Inhibitory Transmitters
Lead to decreased firing in post-synaptic
neuron
Routes of Administration
Inhale
Insuflate
Ingest
Inject
Enema
Contact Absorption (patch)
Drug Ingestion
ORAL
20 to 30 minutes
 INHALING
7 to 10 Seconds
INJECTING
3 to 5 minutes- skin popping
15 to 30 seconds- IV
SNORTING
3 to 5 minutes
CONTACT
Limbic System
Reward
System
Nucleus
accumbens
Prefrontal
cortex
Ventral
tegmental
area
Limbic System
Link between higher cortical activity
and the “lower” systems that control
emotional behavior
Limbic Lobe
Deep lying structures
amygdala
hippocampus
mamillary bodies
Limbic System
Specialized brain areas for
producing and regulating
PLEASURE
Ventral Tegmental Area
Nucleus Accumbens
Prefrontal Cortex
Areas of Limbic system– amygdala,
hippocampus, hypothalamus
Limbic System
Generates primitive emotional
responses to situations
Allows for SURVIVAL
Identify danger/ threats
Fear and aggression
Identify pleasure– “natural
rewards”
Eating
Sex
Social Interaction
R
e
w
a
r
d
P
a
t
h
 VTA and NA
 Primitive brain stem and limbic areas
 Activated by drugs of abuse
 Activation of these primitive areas can
OVERRIDE more evolved cortical areas
Reward Pathway
Also the site of action for addictions
Drugs activate the pathway with force
and persistence not seen with natural
rewards
Drug Effects On
Neurotransmission
Alcohol, heroin, nicotine excite the
dopamine neurons in the VTA to
increase dopamine release
Drug Effects on Cell
Increased cAMP levels
Activation of transcription factor CREB
and changes in gene expression
Changes in synapses, cell structure and
function
The resulting intracellular changes appear
to be the molecular and cellular basis of
addiction (persistent behavioral
abnormalities)
Nestler Am J Addiction 2001; 201-217
Drug Effects on Cell and Learning
Intracellular changes for
addiction the same as for
learning
Both activities share
intracellular signaling cascades
(cAMP) and depend on activity
of CREB
Drug Effects on Cell and Learning
Learning and addiction show
similar changes in neuron
morphology
Similar changes at the level of the
synapse
Multiple similar changes in the
neuron
Long term changes
Addiction is long term
Nestler 2001 Science 292 (5525) pp 2266-67
Drug Effects
on the Cell
 Drugs of abuse all directly or indirectly
increase dopamine binding to post synaptic
receptor with acute behavioral effects
 Chronically, this increases cAMP levels and
leads to a cascade of changed cell activity
Other Chronic Drug Effects
Cell Death
Neurons
don’t grow
back
Alcohol,
ecstasy,
meth
Effect
memory,
mood,
learning
Chronic Drug Effects
Persistent Effects of Drug Use
Amygdala
not lit up
Amygdala
activated
Front of Brain
Back of Brain
Nature Video
Cocaine Video
Brain Imaging
PET
Brain Functioning
Radiolabeled glucose for levels of
activity
Effects of Drugs
Distribution in body
Measure local concentration at binding
sites
Spatial Resolution of 4 mm
Positron Emission Tomography (PET)
NIDA Research
 Overall goal of NIDA
research to:
Reverse the brain changes
that underlie addiction
Roll back the loss of
cognitive and motor
functions that occur
 Develop interventions to
stop brain damage, repair
damage, and retrain the
brain
 Restore brain function after
it has been changed by drug
use
PET Scan
Brighter red
indicates
higher levels
of activity
(glucose
utilization)
Your Brain on Drugs
1-2 Min
3-4
6-7
7-8
9-10
10-20
5-6
8-9
20-30
Your Brain After Drugs
Drugs Have
Long-term
Consequences
Stimulant Studies
London et al. (2004)
PET images of brain activity
 Patients in acute
methamphetamine withdrawal (4 to
7 days)
Patients
10 year history
4 grams per week
 18 days of use out of 30
Stimulant Studies
London et al. (2004)
levels of depression and anxiety
measured
PET Scans
Patient Report
 brain- glucose metabolismdepressed mood, sadness, anxiety,
and drug craving
 Beck’s Depression Inventory
ratings averaged 9.5 for
methamphetamine patients and 1.1
for control
Examples of Brain Studies
Treatment Application
London et al. (2004)
Treatment of Methamphetamine Users
Mood disorder symptoms
may create an acute
barrier to treatment for
methamphetamine
abusers
Stimulant Studies

Treatment Applications from
London’s Stimulant Studies
Implications for treatment
Expect clients to feel poorly
 Treatment engagement strategies should focus
on helping patients to deal with negative
emotional states (Depression and Anxiety)
Avoid counseling techniques that are
confrontational
 Relapse potential is high because clients feel
poorly
Be aware of clients’ turning to self medication
activities to relieve the negative feeling states
Cues for Cocaine and Normal
Pleasures Activate Brain Sites
Childress, 1999
 Cues for Cocaine
 Cocaine abusers may experience a
powerful urge to use when they
encounter environmental cues
associated with use
Limbic regions of the brain are
activated when watching cocainerelated videos
Childress, 1999
Persistent Effects of Drug
As a result of intracellular changes, the
previously cocaine addicted brain has
persistently altered functioning
(craving)
Environmental Cues
Treatment Applications for Childress’
Cue-Induced Cocaine Craving Study

Implications for Treatment
 Understand the importance
environmental cues play in initiating the
craving process
 Review program educational materials to
ensure that potential environmental cues
for drug use are eliminated
Normalize cue and craving responses for
clients
Teach clients how to “urge surf” and to
identify potential environmental cues
Recovery of Dopamine
Transporters
 Pet scan
 shows levels of dopamine transporters
 Lower levels of dopamine transporters were
associated with poorer performance on tests of
memory and motor skills
 Impairments in motor skills and memory continued
 Volkow, et al. 2001
Poor Motor & Memory Performance
 33 year old male- 80 days post detox
Low Severity- Parkinson Disease
 transporter losses may not recover
 Volkow, et al. 2001
Simon, et al. 2002
Cognitive Effects of Stimulants
 Studied 40 current Methamphetamine
Users
Impairments
 memory
 abstract thinking
 changing points of view
 ability to manipulate information
 comprehension deficits
Word recall
Simon, et al. 2002
Cognitive Effects of Stimulants
 Help clients who are mandated into
treatment deal with cognitive problems
associated comprehension
Ensure that clients understand
what counts as compliance with treatment
services
counselor recommendations
consequences for failure to comply
Give concrete, specific information
 Develop methods to help clients
remember treatment recommendations or
medications
Treatment Applications for
Simon, et al.’s study
Treatment Implications:
Drugs’ impact on brain chemistry may
have permanent or long term effects
(impairment 2 years)
Extend length of treatment
Inform/educate client
Structure accessible services
Avoid changing service delivery times
Simplify client paperwork