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Repeated Administration

Addiction Physical and psychological dependence

Tolerance More drug is needed for same effect

Sensitization Same amount of drug induces larger effect

How Does a Drug Work?

Drug Mechanisms

Agonist- Facilitates or

mimics NT

Antagonist- Prevents NT

action

For example:

Drug Effects

Block Action

Potential

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Sites of Drug Action Acetylcholine

Drug Effects Serotonin

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Drug Effects Dopamine

The Reward Pathway

Reward

nucleus

accumbens

Planning

Inhibition

Self-control

Emotional memory

Prefrontal

cortex

amygdala

Ventraltegmental

area

DA

Video-Major Points

All drugs self-

administered

by animals are

also self-administered

by people

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Drug Effects

http://learn.genetics.utah.edu/content/addiction/drugs/mouse.html

Cocaine & Amphetamine

Routes of Administration Behavioral Effects

Autonomic functions

Increase blood pressure

Increase body temperature

Psychomotor stimulant effects Decreased fatigue, Increased arousal

Reduced appetite

Elevated mood (euphoria)

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Changes in Brain Function Drug Effects

Addiction & Release of DA

Time (hours)

Cocaine Self-injectionsTime (hours)

Amphetamine Self-injections

Marijuana

60 Cannabinoids

THC psychoactive agent

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Behavioral EffectsLow to Moderate Doses

Disinhibition, relaxation, drowsiness Exhilaration, euphoria

Sensory - perceptual changes

STM impairment

Balance impaired

Decreased muscle strength

Small tremor

Poor on complex tasks (e.g., driving)

Large Doses

Pseudo hallucinations

Synesthesias

Impaired judgment, slower RT

Pronounced motor deficits

Disorganized thoughts

Confusion

Paranoia

Agitation

Receptor Location

CB1 receptor

Effect on the Brain Drug Effects

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%c

hangeinaccumbensDA

Increase In Dopamine Inhibition and Excitation

Embryonic Development Early Neural Development

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Early Neural Development Early Brain Development

Early Brain Development Rapid Growth

Postnatal

Prenatal

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Steps in Brain Development

1. Neurogenesis

2. Migration

3. Differentiation

4. Synaptogenesis

5. Apoptosis

6. Remodeling

1. Neurogenesis

Starts with Closure of Neural Tube

1. Neurogenesis

Birth-Dating Neurons

BrdU -synthetic

nucleoside-

inserted into DNA

1. Neurogenesis

Ventricular Mitosis

Stem Cell: Genetic Memory For Division

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Adult Neurogenesis

The Olfactory BulbHippocampus

2: Migration

Importance of Radial GliaCell Adhesion Molecules

Radial Migration

Inside-Out Cortical Pattern

Tangential Migration

Interneurons

Aberrant Migration

Dyslexia: A region of the left hemisphere important

for language comprehension

3. Differentiation

Migrating cells immature

Structurally

Functionally

At destination, determined by:

Genetic Blueprint

Proteins

Environmental Signals

From Surrounding Cells

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Induction Experiment 4. Synaptogenesis

Axons

Chemotropic Guidance 4. Synaptogenesis:Myelin

Begins before birth in M1 and S1

Continues into adolescence (frontal lobes)

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4. Synaptogenesis: Dendrites

Usually begins after migrationBegins prenatally, but continues postnatally

5: Apoptosis

Up to 50% neurons born in

1st 7 months die

Neurotrophic Growth Factors

Required for Survival

Brain structure as much

about sculpting as growth

6. Synaptic Remodeling

Max # of Synapses at between 1 and 5 yrs of age

Development Done?

By 5-6 years of

age, 95% of

structural

developmentcomplete

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Nature? Intrinsic factors (genes)

Mutations

Nurture? Extrinsic factors (environment)

Twin studies

What determines development?

Phenylketonuria (PKU)

Enzymatic Disorder

Phenylalanine

IQ < 30

Episodic Seizures

What determines development?

The Teenage Brain The Aged Brain

Normal Aging: Cortical Thinning