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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NAc shell

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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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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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MORPHINE

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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

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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.

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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