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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
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Di Chiara et al., Neuroscience, 1999.
FOOD
MountsIntromissionsEjaculations
Fiorino and Phillips, J. Neuroscience, 1997.
Natural Events Elevate Dopamine Levels
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Female Present
Some drugs activate your reward systems since they act on the same receptors
Drugs make your brain really happy…..
Normal Brain Brain on Drugs
BUT only when your brain is on drugs.
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Accumbens AMPHETAMINE
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MORPHINE
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NICOTINE
Di Chiara and Imperato, PNAS, 1988
Effects of Drugs on Dopamine Release
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!
Upregulation
Downregulation
Homeostatic Changes to Postsynaptic Receptor Density as a Function of the Amount of Neurotransmitter Released
Brain on drugs after tolerance
Brain on drugs for an extended
period
Chronic drug taking ….reorganizes the liking and wanting systems
… drugs may no longer be pleasurable but you still want them…
Drugs can change your brain so that natural events are no longer pleasurable
Normal
Addicted
The brain now has a disease… it’s a different brain under constant stress
When the “switch” gets flips depends on ….
your brain chemistry….
your drug history….
your drug history….
and other factors
Even 80 days following detox, a methamphetamine user’s dopamine transporter system (right) hasn’t
recovered to normal levels (left)
Normal
Cocaine Abuser (10 da)
Cocaine Abuser (100 da)
Cocaine has long lasting effects
At high enough doses, Ecstasy destroys nerve fibers
high
low
High DA receptor
Low DA receptor
DA Receptors and the Response to Methylphenidate (MP)
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.
Dop
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leve
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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
Mu receptor distribution5HT1a receptor distribution
Cerebral Cortex
Frontal lobe
Parietal lobe
Occipital lobe
Temporal 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