NEUR200 - Exam 1 Material

what is a neurotransmitter?

a chemical released by terminal button; has an excitatory or inhibitory affect on another neuron

NT must meet what 3 criteria?

1. has o be present at the terminal buttons of a presynaptic neuron

2. has to be calcium dependent (released due to an A.P/depolarization)

3. receptors have to be present on the postsynaptic cell

What are the 3 major classes of NTs?

Small molecules, peptides, and lipids/gasses

What is a neuromodulator?

a substance that does not exactly like a NT; they might enhance, reduce, or prolong the effect of a standard NT

a peptide acts like a … when packaged with a …

a peptide acts like a neuromodulator when packaged with a NT

What are the 6 major (small molecule) NTs?

Acetylcholine, Dopamine, Norepinephrine/Epinephrine, Serotonin, Glutamate, GABA

Which of the major NTs are amines?

Dopamine, Norepinephrine/Epinephrine, and Serotonin

Which of the major NTs are amino acids?

Glutamate and GABA

What are the 2 Acetylcholine Receptors?

1. Nicotonic (ionotropic) receptor

2. Muscarinic (metabotropic) receptor

Acetylcholine function(s)

• released at the neuromuscular junction for contraction/activity of smooth and skeletal muscle

• plays a role in memory; decreased ACh is associated with alzheimers

Agonist

a drug that mimics the effect of a NT

Antagonist

a drug that inhibits the NT from binding at its site but has NO EFFECT

effect of Acetylcholine antagonists

inhibit muscle contraction/induce muscle paralysis

effect of Acetylcholine agonists

promotes ACh release

What are Autoreceptors?

NT-specific receptors on the presynaptic cell that take up the same NT that the cell releases (ultimately inhibiting NT release)

What kind of autoreceptor does ACh have?

muscarinic autoreceptors

What are Transporters?

transports NT back into the presynaptic membrane

What is the transporter for ACh called?

Choline transporter

What are Vesicular Transporters?

transports NTs back into vesicles in the presynaptic cell

What is the vesicular transporter for Ach called?

VAChT

Dopamine is taken in through what foods?

hard cheese and bananas

Dopamine function(s)

• voluntary muscle movment

• attention

• learning

• reinforcement

• planning

• problem-solving

Too little DA is associated with… and too much DA is associated with…

too little → Parkinsons

too much → Schizophrenia

Describe the synthesis of Dopamine (starting with tyrosine)

1. Tyrosine hydroxylase breaks down into L-DOPA

2. L-DOPA become dopamine

Norepinephrine and Epinephrine can be synthesized by…

the Dopamine pathway; DA beta hydroxylase breaks dopamine into norepinephrine and then into epinephrine

Which step in the synthesis of dopamine is rate limiting?

the breakdown of tyrosine by tyrosine hydroxylase

What are the two major pathways of Dopamine?

1. Nigrostriatal DA pathway

2. Mesolimbic DA pathway

The degneration of which DA pathway causes parkinsons?

the nigrostriatal pathway

Describe the Nigrostriatal DA pathway

involved areas: the caudate nucleus and substantia nigra

function: maintains motor behavior

Describe the Mesolimbic DA pathway

involved areas: prefrontal cortex, amygdala, nucleus accumbens, ventral tegmental area

function: responsible for reward/pleasure

What are the 5 Dopmaine Receptors?

D1-D5 are all metabotropic receptors

DA transporter is called…

DAT (in the presynaptic cell)

DA vesicular transporter is called…

VMAT

Norepinephrine/Epinephrine function(s)

related to learning, ADHD, depression, organizing movements involved areas: Locus Coeruleus

What are the Norepinephrine and Epinephrine receptors?

alpha or beta metabotropic adrenergic receptors

The Norepinephrine/Epinephrine transporter is called…

NET

The vesicular transporter for Norepinephrine/Epinephrine is…

VMAT

Serotonin function(s)

• regulates mood, pain, arousal, and sleep

• involved areas: cortical areas, nucleus accumbes, raphe nuclei, pons and medulla

Describe the synthesis of Serotonin

tryptophan is broken down by tryptophan hydroxylase into 5-HTP which is then broken down into 5-HT by 5-HTP Decarboxylase

The rate limiting step in Serotonin synthesis is…

the breakdown of tryptophan into 5-HTP by tryptophan hydroxylase

What are the receptors for Serotonin?

5-HT receptors (metabotropic and ionotropic); 14 types

The Serotonin transporter is called…

SERT

the vesicular transporter for Serotonin is…

VMAT

LSD does what to Serotonin?

acts as an agonist (mimics its effect)

Ecstasy does what to Serotonin?

is taken up by 5-HT transporters which causes 5-HT release instead of re-uptake (enhances serotonin activity)

Glial cells store which NTs?

GABA and Glutamate

What type of NT is GABA? About what percentage of it is in the brain?

inhibitory (30-40% GABA in brain)

What type of NT is Glutamate? About what percentage of it is in the brain?

excitatory (50% Glutamate in brain)

What’s the effect of caffeine on GABA?

inhibits GABA activity

What’s the effect of alcohol on GABA?

increases GABA activity

What’s the effect of tranquilizers on GABA?

increases GABA activity

What’s the effect of caffeine on Glutamate?

increases Glutamate activity

What’s the effect of alcohol on Glutamate?

decreases Glutamate activity

What’s the effect of PCP “angel dust” on Glutamate?

increases Glutamate activity

What are the Glutamate receptors?

AMPA, NMDA, and Kainate (ionotropic)

and mGLuRs (metabotropic)

Glutamate transporters are called…

EAATs

Glutamate vesicular transporter is…

VGLUT

What are the GABA receptors?

GABA a (ionotropic) and GABA b (metabotropic)

the GABA transporter is called…

GAT

the GABA vesicular transporter is called..

VGAT or VIATT

Drug action process

Route of administration → absorbption/distribution → binding → inactivation → secretion

What are the 4 types of administration?

Oral (the slowest!), Absorption, Inhalation (faster), and Injection (fastest)

Absorption routes

sublingual, intranasal, ocular, intrarectal

What are the types of injections?

intravenous (fastest), intraperitoneal, intramuscular, subcutaneous, intradermal (slowest)

What is the most important factor that determines the rate at which a drug in the bloodstream reaches sites of action in the brain?

lipid solubility (higher lipid solubility = better drug diffusion)

Drug absorption depends on what two factors?

diffusion across the membrane (blood brain or placental barrier) and drug concentration

What’s the structure of typical capillary?

endothelial cells that make up the capillary have spaces in b/w them

What’s the structure of the blood brain barrier? What can go through?

glial cells cover spaces between endothelial cells

• small molecules can pass through (O2 and CO2)

• lipid soluble molecules can pass through

• water soluble molecules CANNOT pass through

What does a Dose Response Curve show?

a graph of the magnitude of an effect of a drug ( x-axis = dose of drug y-axis = effect)

• helps determine a safe and effective dosage

What is the Effective Dose 50 (ED₅₀)?

the dose of drug that produces desired effect in 50% of people

What is the Toxic Dose 50 (TD₅₀)?

dose of drug that produce toxic effects in 50% of people

What is the Lethal Dose 50 (LD₅₀)?

dose of drug that is lethal in 50% of people

What is the Therapeutic Index (TI)?

the measure of a drugs margin of safety

TI = TD₅₀/ED₅₀

What does a lower TI mean? What does a higher TI mean?

lower TI = greater risk of toxicity

higher TI = less risk of toxicity

(a higher TI is better)