Lectures # 3 & 4

Question 1

What is state-dependent learning?

Answer 1

• **State-dependent learning: **Task learned in a particular state will be better performed later if in the same state in which it was learned
• Opposition hold ture as well
• Not only true for drug use, but also emotional states and environments

Question 2

What are dose-response curves?

Answer 2

**Dose-response curves **describe extent of effect (response) produced by a given drug concentration (dose)

Question 3

What is threshold dose?

Answer 3

**Threshold dose: **smallest dose that results in measureable effect

Question 4

What is ED50?

Answer 4

ED50 (50% effective dose): dose that produces half the maximal effect

Question 5

What is maximum response?

Answer 5

**Maximum response: **all receptors occupied (can’t take any more…)

Question 6

How can dose-response curve help? how can we see differnces in potency?

Answer 6

• We can compare various drugs in terms of dose-response curve
• Differences in potency shown by differences in ED50

Question 7

What is potenc?

Answer 7

Potency:absoluted amount of drug needed to produce specific effect

Question 8

What is TD50?

Answer 8

TD50 (50% toxic dose): dose at which 50% of the population experiences a toxic effec

Question 9

What is the therapeutic index? Which is safest a high or low TI?

Answer 9

The Theraupetic index (TI)= TD50/ED50

A large TI indicates a safe drug

A small TI indicates an unsafe drug

Question 10

What is pharmacogenetics?

Answer 10

**Pharmacogenetics **is the study of the genetic basis for variability in drug response among individuals. Goal: identify genetic factors that result in susceptibility to specific side effects, or predic theraupetic response.

Question 11

What is genetic polymorphisms?

Answer 11

• **Genetic polymorphisms **for drug-metabolizing enzymes contribute to variability in metabolism.
• Genetic variation in drug-metabolizing enzymes has been the most studied.

Question 12

What is cytochrome P450 (CYP450)?

Answer 12

The cytochrome P450 enzyme family are responsible for oxidizing most psychoactive drugs. The cytochrome P450 enzyme family genes have many polymorphisms that affect drug levels.

Question 13

What is pharmacodynamics?

Answer 13

**Pharmacodynamics: **study of the physiological and biochemical interaction of drug molecules with cell receptors in target tissue.

Question 14

What are receptors?

Answer 14

**Receptors **are proteins on cell surfaces or within cells

Question 15

What is a ligand? What does this have to do with receptors?

Answer 15

**Ligand: **molecule that binds to a receptor with some selectivity.

Receptors have specificity for ligands due to their molecular shapes.

Question 16

What is a receptor agonist?

Answer 16

**Receptor agonist: **has best chemical “fit” (highest affinity); attaches readily ot the receptor and produces significant biological effect.

Question 17

What is a receptor antagonists?

Answer 17

Receptor antagonists also fit receptors but produce no cellular effect ( low efficiancy)

Question 18

Can drugs as agonists?

Answer 18

• Yes
• Drugs can:
  
  • Increase neurotransmitter synthesis or release
  • Prolonging action of the neurotransmitter within the synapse

Question 19

What is a synapse?

Answer 19

In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another cell (neural or otherwise).

Question 20

What are neurotransmitters?

Answer 20

Neurotransmitters areendogenous chemicals that send out signals across asynapse from one neuron(brain cell) to another ‘target’ neuron. They are packaged into synaptic vesicles clustered underneath the membranein the axon terminal located at the presynaptic surface of a synapse.

Question 21

Is **ligand-receptor binding **forever? What does it do?

Answer 21

• **Ligand-receptor binding **is temporary. After ligand separates, the receptor is free to bind again.
• Ligand binding causes change in receptor shape that initiates a series of events in the cell.
  
  • These event are overall exicitatory or inhibitory.

Question 22

Are receptors forever?

Answer 22

Receptor proteins have a particular life span; the number and sensitivity of receptors can also change.

Question 23

What is up-regulation?

Answer 23

**Up-regulation: **number of receptors increases

Question 24

What is down-regulation?

Answer 24

**Down-regulation: **number of receptors is reduced in response to absence of ligands or chronic activation.

Question 25

Are all receptors the same? why is this important?

Answer 25

* **Receptor subtypes: **receptors with different characteristics in different tissues * A particular drug may have effect on multiple subtypes, some of which have desired effect and others undesired effects

Question 26

What is a goal of neuropharmacology? hint: involves receptors

Answer 26

A goal of neuropharmacology- design drugs that bind with greater affinity to one receptor subtype to initiate selective effect, but not act on related receptor subtypes to avoid extra side effects.

Question 27

What are **neurons**?

Answer 27

* **Neurons** are one of the two primary cell types in the nervous system. * Neurons transmit information through electrical signaling

Question 28

What are the functions of glial cells?

Answer 28

* are non-neuronal cells that maintain homeostasis, formmyelin, and provide support and protection forneurons in the brain and peripheral nervous system. * glial cells have various functions, including metabolic support, protection, and insulation for neurons

Question 29

What do neurons do will the information?

Answer 29

* Collect input * drugs can alter or create input * Process/decide in some way * Produce output

Question 30

How many types of neurons are there? list them:

Answer 30

3 main types of neurons Sensory neurons, interneurons, and motor neurons

Question 31

What are **sensory neurons**?

Answer 31

**Sensory neurons **transform stimuli outside the body into electrical signals.

Question 32

What are **interneurons**?

Answer 32

* **Interneurons:** neurons in brain and spinal cord that form neural circuits * responsible for all non-sensory processing (memory, cognition, decision-making, conscious sensation)

Question 33

What are **motor neurons?**

Answer 33

**Motor neurons **transfer electrical signals into muscle movement.

Question 34

What are the parts of a neuron?

Answer 34

soma, dendrites and axon

Question 35

What is the **soma**?

Answer 35

**Soma- **cell body; contains nucleus and other organelles.

Question 36

What are the **dendrites**?

Answer 36

**Dendrites- **projections form the soma that receive information.

Question 37

What is the **axon**?

Answer 37

**Axon-** extension that conducts electrical signals from the cell body to the terminal buttons.

Question 38

What is **convergence**?

Answer 38

**Covergence: **information coming from a vast number of neurons all comes together into a single neuron.

Question 39

What is **divergence**?

Answer 39

**Divergence: **information from one neuron may be passed on to thousands of others

Question 40

How do neurons communicate? hint: very long

Answer 40

Neurons releases neurotransmitter from axon terminal that travels across synapse and contacts receptor on dendrite of another neuron, making that next neuron more (or less) likely to relase a neurotransmitter that would have an effect on the next neuron, etc... The process that results in a neuron firing a neurotransmitter is known as an action potential.

Question 41

What is the soma #2?

Answer 41

Soma * cell body * metabolic machinery

Question 42

What are the dendrites #2?

Answer 42

* Dendrites: * Receive input from neurons at synapses (post synaptic)

Question 43

What are axons #2?

Answer 43

* Axons * Before synapse (presynaptic) * Originates at Axon Hillock * Often insulated with Myelin sheaths * Ends at presynaptic terminal button * Release neurotransmitters

Question 44

What's so imporant about the synapse?

Answer 44

* The synapse is a critical point, hence synaptic transmission * It is only space, but very important space * One neuron releases a messege (neurotransmitter) into the space, another neuron receives this message (receptor) * Thousands of receptors on the dendrites and soma * Effect through receptor may be excitatory or inhibitory

Question 45

Is the structure fixed?

Answer 45

* NO * Prolonged synaptic activity can also change the number, size, and shape of dendritic spines * These changes occur throughout life and permit us to continue to learn new associations * Patients with mental impairments have fewer or smaller dendritic spines

Question 46

What are gated channels?

Answer 46

Ion channels are specific for one of a few ions. **Gated channels **are normally closed; open in response to specific stimuli: * Ligand-gated channel * Voltage-gated channel

Question 47

How do **ligand-gate channels** work?

Answer 47

**Ligand-gated channel- **opens when a ligand binds to a receptor.

Question 48

How do **voltage-gated channel** work?

Answer 48

**Voltage-gated channel-** opens when the electrical potential across the membrane is altered.

Question 49

What is the importance of second-messenger systems?

Answer 49

Some ion channels are modified by second messengers which cause intracellular phophorylation (addition of a phosphate group) and regulate the state of the channel.

Question 50

how does neuronal signaling work?

Answer 50

* Output from axon terminals * Input contact at dendrites (or cell body) * So what are the effects these nerutransmitter have, and how do they make another neuron release neurotransmitters from its terminal (or not) * Effect through receptor * Lock and Key analogy

Question 51

What happens to neurotransmitters?

Answer 51

* Synthesized by presynaptic neuron * Transported to axon terminal * Stored in vesicles * Bind with postsynaptic neuron * What about the one that don't bind? * Active reuptake * Enzymatic breakdown * Diffusion

Question 52

What are the two main receptor types?

Answer 52

* Directly coupled receptor (ionotropic) * After binding, structural change opens opens pore, lets in ions * Indirectly couple receptor (metabotropic) * After binding, series of intracellular biochemical evetns leads to signal that opens ion channels

Question 53

How does binding work (overview)?

Answer 53

* Neuron receives neurotransmitter at receptor * Signals change membrane of postsynaptic neuron * Changes in flow of electrical currents * Neuron integrates signals * Triggers action potential * Tracels down axon * Release neurotransmitter * back to the top -\>

Question 54

What is the action potential?

Answer 54

* The action potential is when electrical charge travels leght of axon * Reults in firing at axon terminal * Happens when total charge inside cell is above threshold at axon hillock (trigger zone) * Threshold is -50 mV * When hits, voltage-gated Na+ channels open

Question 55

What is the Action potential #2?

Answer 55

* The firing of a neuron is an electrical event * To understand the action, potential we need to understand the electrical charges in and around the neuron

Question 56

What is the resting potentinal?

Answer 56

* The **resting membrane potential **is the difference in electrical charge (-70 millivolts) * -70 mV results in being **polarized** * More negative inside, more positive outside * Naturally, electrical charges move towards equilibrium (electrical gradient) * So, if move towards equilibrium, what happens if ions could move freely in and out of the cell?

Question 57

What are neural membranes?

Answer 57

Lipid bylayer- will not dissolve Barrier to ions, proteins and other molecules

Question 58

Distribution of ion in and outside the cell comparison:

Answer 58

* Na+ * outside: 440 * inside: 50 * K+ * outside: 20 * inside: 400 * Cl- * outside: 560 * inside: 40-150 * Ca2+ * outside: 10 * inside: .0001

Question 59

What about chemical gradient?

Answer 59

* Chemical gradient is similar but for the particualr molecule, regardless of charge * In other words, equilibrium for sodium, potassium, calcium, etc.

Question 60

What about equilibrium both electrical and chemical?

Answer 60

* With potassium, when the electrical and chemical gradients are balanced, the inside of the cell is more negative (-70mV) * The **Na+-K+ pump** moves 3 Na+ outside for every 2 K+ moved inside, keeping inside negative. Ions pumped against concentration gradients; requires energy. * The resting potential sets the stage for action potential.

Question 61

Synaptic Transmission

Answer 61

Neurotransmitters (chemical) Cause either depolarization (excitation, EPSP) or hyperpolarization (inhibition, IPSP)