L04 Slides

Repeated Administration

How Does a Drug Work?

Addiction •

Physical and psychological dependence

Tolerance •

More drug is needed for same effect

Sensitization •

Same amount of drug induces larger effect

Drug Mechanisms •

•

Agonist- Facilitates or mimics NT

For example:

Drug Effects Block Action Potential

Antagonist- Prevents NT action

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Sites of Drug Action

Acetylcholine

Drug Effects

Serotonin

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Drug Effects

Dopamine

The Reward Pathway

Video-Major Points

Prefrontal cortex

Ventral tegmental area

Planning Inhibition Self-control

nucleus accumbens

Reward

DA

All drugs selfadministered by animals are also selfadministered by people

amygdala

Emotional memory

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Drug Effects

Cocaine & Amphetamine

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

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

Marijuana 60 Cannabinoids THC psychoactive agent

Time (hours) Cocaine Self-injections

Time (hours) Amphetamine Self-injections

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Behavioral Effects Low 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)

Receptor Location CB1 receptor

Large Doses • Pseudo hallucinations • Synesthesias • Impaired judgment, slower RT • Pronounced motor deficits • Disorganized thoughts • Confusion • Paranoia • Agitation

Effect on the Brain

Drug Effects

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Inhibition and Excitation

% change in accumbens DA

Increase In Dopamine

Embryonic Development

Early Neural Development

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Early Neural Development

Early Brain Development

Early Brain Development

Rapid Growth Prenatal Postnatal

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Steps in Brain Development 1. 2. 3. 4. 5. 6.

1. Neurogenesis Starts with Closure of Neural Tube

Neurogenesis Migration Differentiation Synaptogenesis Apoptosis Remodeling

1. Neurogenesis Birth-Dating Neurons

1. Neurogenesis Ventricular Mitosis Stem Cell: Genetic Memory For Division

BrdU -synthetic nucleosideinserted into DNA

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Adult Neurogenesis The Olfactory Bulb

Hippocampus

Aberrant Migration Dyslexia: A region of the left hemisphere important for language comprehension

2: Migration Importance of Radial Glia Cell Adhesion Molecules Radial Migration Inside-Out Cortical Pattern Tangential Migration Interneurons

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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5: Apoptosis

4. Synaptogenesis: Dendrites Usually begins after migration Begins prenatally, but continues postnatally

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

Development Done?

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

By 5-6 years of age, 95% of structural development complete

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What determines development? •

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Nature? Intrinsic factors (genes) • Mutations Nurture? Extrinsic factors (environment) • Twin studies

The Teenage Brain

What determines development? •

Phenylketonuria (PKU) • Enzymatic Disorder • Phenylalanine • IQ < 30 • Episodic Seizures

The Aged Brain Normal Aging: Cortical Thinning

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