Brain Basics
BRAIN ON DRUGS?
What is your nervous system?
Neurons “communicate” with each other using
neurotransmitters
Neurotransmitters convey “messages” across the synapse
Dopamine/Opioids: Brain’s incentive reward systems
Activation of reward center produces a “wanting” and “liking”
response
Natural events activate these reward systems
Natural Events Elevate Dopamine Levels
SEX
FOOD
% of Basal DA Output
NAc shell
150
100
Empty
50
Box Feeding
200
150
100
15
10
5
0
0
0
60
120
Time (min)
Di Chiara et al., Neuroscience, 1999.
180
Copulation Frequency
DA Concentration (% Baseline)
200
Female Present
Sample
Number
1
2
3
4
5
6
7
8
Fiorino and Phillips, J. Neuroscience, 1997.
Mounts
Intromissions
Ejaculations
Some drugs activate your reward systems since they act
on the same receptors
Drugs make your brain really happy…..
BUT only when your brain is on drugs.
Normal Brain
Brain on Drugs
Accumbens
1100
1000
900
800
700
600
500
400
300
200
100
0
AMPHETAMINE
DA
DOPAC
HVA
250
1
2
3
4
Time After Amphetamine
% of Basal Release
400
0
Accumbens
Caudate
150
100
0
0
1
2
3 hr
Time After Nicotine
COCAINE
DA
DOPAC
HVA
200
100
0
5 hr
0
NICOTINE
200
Accumbens
300
250
% of Basal Release
% of Basal Release
% of Basal Release
Effects of Drugs on Dopamine Release
1
2
3
4
Time After Cocaine
Accumbens
5 hr
MORPHINE
Dose (mg/kg)
0.5
1.0
2.5
10
200
150
100
0
0
1
2
3
4
Time After Morphine
5hr
Di Chiara and Imperato, PNAS, 1988
Repeated use of drugs trigger compensatory processes
and saturate the brain’s reward systems
 individual can become conditioned/habituated/adapted to
the intense level of drug-induced pleasure (develops tolerance
or sensitization)
 the normal level of natural rewards are no longer
experienced as very pleasurable, and
 after chronic use, the brain’s reward systems becomes so
changed that nothing is pleasurable – not even the drugs!
Homeostatic Changes to Postsynaptic Receptor Density as a Function
of the Amount of Neurotransmitter Released
Upregulation
Downregulation
Chronic drug taking ….reorganizes the liking
and wanting systems
Brain on drugs after
tolerance
Brain on drugs for
an extended period
… drugs may no longer be pleasurable but you still want them…
Drugs can change your brain so that natural events are no longer
pleasurable
The brain now has a disease… it’s a different brain under
constant stress
Addicted
When the “switch” gets flips
depends on ….
your brain chemistry….
your drug history….
your drug history….
Normal
and other factors
Even 80 days following detox, a methamphetamine
user’s dopamine transporter system (right) hasn’t
recovered to normal levels (left)
Cocaine has long lasting effects
Normal
Cocaine Abuser (10 da)
Cocaine Abuser (100 da)
At high enough doses, Ecstasy destroys nerve
fibers
DA Receptors and the Response to
Methylphenidate (MP)
Low DA
receptor
high
low
Dopamine receptor level
High DA
receptor
As a group, subjects with low receptor levels found MP pleasant
while those with high levels found MP unpleasant
Adapted from Volkow et al., Am. J. Psychiatry, 1999.
Drugs not only affect the brain, but also affect the body
Gross Brain Anatomy
Forebrain
Midbrain
Hindbrain
(Brainstem = Midbrain + Hindbrain - Cerebellum)
Hindbrain
• Medulla
• Pons
• Cerebellum
Medulla
• caudal end of brainstem; rostral end of spinal cord
• connects rest of brain to spinal cord
• life support functions (heart rate, respiration)
Pons
• ventral side of cerebellum
• levels of consciousness, sleep,
• arousal, control of autonomic
functions,
• sleep, relay info to cerebellum
Cerebellum
• coordination of voluntary
movement
• learning motor behaviors
• involved in cognition
• timing of motor output
Midbrain
• rostral end of brainstem: reticular formation, superior/inferior
colliculi
• arousal, wakefulness
• information modulation
• source cells for some important neurotransmitters (biogenic amines)
Forebrain
•
•
•
•
•
Cerebral Cortex
Thalamus
Hypothalamus
Basal Ganglia
Limbic System
Thalamus
• relays information from diverse areas
to cerebral cortex
• integrates sensory information
• regulates sleep-wakefulness
Hypothalamus
• homeostatic control (e.g. body
temperature, cardiovascular system,
food and water intake)
• regulates autonomic and endocrine
systems
• Infundibulum connects
hypothalamus to pituitary glands
Basal Ganglia
• voluntary movement, posture
Limbic System
• Medial Forebrain Bundle
– collection of various nerves
running upstream through
midbrain
– involved in reinforcement
• Hippocampus
• Amygdala
• Nucleus Accumbens
Hippocampus
• medial side of temporal lobe
• consolidation of short term memory into more permanent
memory
• recollection of spatial relationships
Amygdala
• inferior medial temporal lobe
• emotional feelings, fear, behavior, perception
Nucleus Accumbens
• very important in
reinforcement and
addiction
• regulation of
movement
• cognitive aspects of
motor control
5HT1a receptor distribution
Mu receptor distribution
Cerebral Cortex
Frontal lobe
Parietal lobe
Temporal lobe
Occipital lobe
Occipital Lobe
• vision
Parietal Lobe
• body sensation (touch, pain, etc.)
• speech reception
• spatial relationships
Temporal Lobe
•
•
•
•
hearing
memory
emotion
vision
Frontal Lobe
•
•
•
•
planned motor behavior
speech production
higher cognition
social reasoning