Biopsych Lecture 4

Front 1

Name/describe two types of receptors

Back 1

Ionotropic/ligand gated ion channels - have an ion channel that opens when a transmitter binds

Metabotropic Receptors - activate G proteins with transmitter attachment, alpha unit attaches to other channel. Slower

Front 2

Function of ligands

Back 2

bind to receptors
activate receptors
block receptors

Front 3

Name/describe 2 main groups of ligands

Back 3

Endogenous (natural body chemicals) - neurotransmitters, hormones (gaba, glu, dopamine)

Exogenous - outside the body - drugs, toxins (activates same receptor as EG NT)

Front 4

Chemicals that fit the cholinergic receptor can be (2 types)

Back 4

Antagonists - block ACh receptors (curare and bungarotoxin)

Agonists - mimic ACh (nicotine)

Front 5

Morphine interacts with what receptor?

Back 5

endogenous opiate receptors

Front 6

What do antagonists do?

Back 6

1) competitive antagonist blocks same site as endogenous transmitter

2) Transmitter binds, but does not activate (it's blocked)!!

OR

Noncompetitive antagonist binds to another site, transmitter binds but cannot activate since it's blocked

Front 7

Three important characteristics about drug targets

Back 7

1) Drugs are ligands that act upon specific receptors
2) Drugs can target one or a few receptor subtypes
3) Since receptor subtypes can have different localizations and functions, drug actions can have widely varying effects

Front 8

Define "drugs"

Back 8

Substances with pronounces effects in small quantities, interacting with receptors or metabolic processes related to synaptic transmission

Front 9

the dose response curve shows

Back 9

Relationship between drug dose and effects (+ drug = + effect, levels out)

ED50 is lower on more potent drug

Graphed as Log dose VS Response

Front 10

Lock and key model

Back 10

each hormone/NT/drug has one place to fit

Front 11

Name potential sites of action - Presynaptic (8)

Back 11

1. Interfere with syntehsis of NT
2. Block AP from going into terminal (ex: block vgated Na+ channels)
3. Block axonal transport of resources into terminal???
4. Disrupt normal NT release (block Ca++ channels, deplete NT?)
5. Interfere w/ packaging of NT into vesicles (ex: leaky vesicles)
6. Modulate (enhance/block) NT release (blocking presynaptic receptors so they can't inhibit??)
7. Interfere with presynaptic reuptake of neurotransmitters
8. Block normal breakdown of NT (ex: mess with enzymes)

Front 12

Name potential sites of action - Post-synaptic (5)

Back 12

1. Degradation of transmitter (prolong effects, don't break NT down)
2. Alter # of postsynaptic receptors
3. Blockade (antagonize) of receptors
4. Activate receptors
5. Interfere w/ metabotropic signaling cascade (2nd messenger/Gprotein)?

Front 13

Why do we care about all these sites?

Back 13

Drugs are important for health and illness

Many drugs are abused. Sites of action offer
insight to understand abuse mechanisms and
may offer potential treatment clues

Drugs are hard to deliver and target accurately. Alternative action locations may facilitate therapeutic applications

Front 14

Name 4 types of NT and examples of each

Back 14

1) Amine NT - acetylcholine, dopamine, seratonin
2) Amino acid NT - GABA, glutamate
3) Peptide NT - Substance P, small chain of Amino acids
4) Gas NT - NO

Front 15

Important facts about Acetylcholine

Back 15

First NT discovered (in heart)

Source neurons in basal forebrain w/widespread projections to cortex and subcortical brain regions

Alzheimer's = loss of ACh

It's important for memory and learning, attention

Created in basal forebrain and peduncolopontine nucleus (small nuclei deep in brain)

Front 16

Name two types of ACh receptors??

Back 16

1) Nicotonic - most are ionotropic and excitatory (muscles receptors, curare can paralyze)

2) Muscarinic - metabotropic type, either excitatory/inhibitory
Muscarinic blockade by scopolamine (seasickness) changes cognition

Front 17

Nicotine effects

Back 17

Increases heart rate, blood
pressure, hydrochloric acid
secretion, and bowel activity Agonist on nicotinic ACh receptors in the ventral tegmental area (reward region)

Front 18

Monoamines (types , where they are located, function)

Back 18

Domamine, Seratonin, Norepinepherine

Located in small nuclei of midbrain
Have widespread projections in brain

Role in movement/reward mechanisms

Front 19

Function of noradregenic pathways

Back 19

Modulate mood, arousal, sexual behavior

Front 20

Function of seratonergic (5-HT) pathways

Back 20

Sleep, sexual behavior, anxiety, etc. Anti-depressents increase 5HT activity

Front 21

Glutamate/Asparate

Back 21

•Glutamate is the most common transmitter in the brain – no particular pathway

• Glutamate acts on AMPA,kainate, and NMDA receptors as well as mGluRs, which are slower metabotropic receptors

• Glutamate can be toxic removed from the synapse by glial astrocytes

Can cause damage, like in strokes and huntingtons disease (too much glu overactivates neurons so they burn out)

Front 22

GABA/Glycine

Back 22

• Inhibitory transmitters widespread in brain and spinal cord

• GABAA–ionotropic, producing fast, inhibitory effects

• GABA agonists, like Valium, are potent tranquilizers

Front 23

Peptide transmitters

Back 23

Small protein peptides

• Numerous types often co-released with other transmitters
• Typically slow actions (i.e., thought to be modulatory)
• Endogenous form of opioids i.e., they are naturally occurring “opiates” –like “unnatural” morphine
• They act at endogenous opioid receptors of various types in brain and gut

Front 24

Endocannibinoid (THC)

Back 24

Brian contains Endocannibinoid (ex: anadamine) and receptors

• Alters memory formation
• Appetite stimulation
• Reduced pain sensitivity
• Protection from excitotoxic brain damage

Front 25

Dopamine has a role in...

Back 25

reward, drug abuse

Experiment w/ animals self administering
(using microdialysis tube w/semiperm membrane and normal salt concentration in nucleus accumbens, measure)

Dopamine release increases with self administration of cocaine

Front 26

Drugs stats

Back 26

(See graph, probably don't need to memorize)

Full time college students more likely to binge drink

Front 27

Study

Back 27

Charts of drug spread in brain

Front 28

Benzodiazapene

Back 28

agonist tranculizer, has binding site on GABA

Front 29

Picrotoxin

Back 29

Poison that blocks gaba receptor , has binding site on GABA

Front 30

Barbituates

Back 30

Sedating drugs w/ binding site on GABA

Front 31

Explain GABA alosteric modulation **

Back 31

Steroid binds to GABA receptor (with GABA already attached), enhances effects so channel is more open

Causes IPSP/prevents EPSPs -drags down to resting potentials

Benzodiazapene/barbiturates also work this way??

Front 32

Inverse agonists

Back 32

causes channel to do opposite of what it does

(ex:on benzodiazapene site to make it anxiogenic - treats overdoses)

Front 33

Binding affinty

Back 33

how strongly attached a drug/NT is, how long it stays

Front 34

Describe the dopamine projections

Back 34

1) Mesolimbocortical pthwy: VTA to nucelus accumbens, cortex, hippocampus

2) Mesostriatial pthwy: substantia nigra to striatium (caudate and putamen)

Front 35

The striatium is made up of...

Back 35

the caudate and putamen

Front 36

Describe noradrenergic pathway

Back 36

Created in lateral tegmental area, spreads to:
1) cerebellum
2) locus corulus (to hippocampus, basal ganglia, cortex)
3) spinal cord

Front 37

Describe the seratonergic (5HT) pathway

Back 37

Created in raphe nuclei, spreads to:
1) Mesencephalic serotenergic cells, which project to thalamus, hypothalamus, basal ganglia, cortex

2) to spinal cord
3) to cerebellum
4) to hippocampus

Front 38

L-dopa

Back 38

drug that causes cells to Increase dopamine production
This is the main treatment options, but it wears off

Front 39

What disorder is linked with dopamine?

Back 39

Dopamine dies in parkinsons, so treatment is to administer dopamine agonists. May have bad side effects (gambling, etc) since it alters the reward system

Substantia nigra dies in parkinsons

Front 40

GO OVER

Back 40

MOUSE PARTY + PATHWAYS!!