Lectures # 3 & 4 Flashcards
What is state-dependent learning?
- **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
What are dose-response curves?
**Dose-response curves **describe extent of effect (response) produced by a given drug concentration (dose)
What is threshold dose?
**Threshold dose: **smallest dose that results in measureable effect
What is ED50?
ED50 (50% effective dose): dose that produces half the maximal effect
What is maximum response?
**Maximum response: **all receptors occupied (can’t take any more…)
How can dose-response curve help? how can we see differnces in potency?
- We can compare various drugs in terms of dose-response curve
- Differences in potency shown by differences in ED50
What is potenc?
Potency:absoluted amount of drug needed to produce specific effect
What is TD50?
TD50 (50% toxic dose): dose at which 50% of the population experiences a toxic effec
What is the therapeutic index? Which is safest a high or low TI?
The Theraupetic index (TI)= TD50/ED50
A large TI indicates a safe drug
A small TI indicates an unsafe drug
What is pharmacogenetics?
**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.
What is genetic polymorphisms?
- **Genetic polymorphisms **for drug-metabolizing enzymes contribute to variability in metabolism.
- Genetic variation in drug-metabolizing enzymes has been the most studied.
What is cytochrome P450 (CYP450)?
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.
What is pharmacodynamics?
**Pharmacodynamics: **study of the physiological and biochemical interaction of drug molecules with cell receptors in target tissue.
What are receptors?
**Receptors **are proteins on cell surfaces or within cells
What is a ligand? What does this have to do with receptors?
**Ligand: **molecule that binds to a receptor with some selectivity.
Receptors have specificity for ligands due to their molecular shapes.
What is a receptor agonist?
**Receptor agonist: **has best chemical “fit” (highest affinity); attaches readily ot the receptor and produces significant biological effect.
What is a receptor antagonists?
Receptor antagonists also fit receptors but produce no cellular effect ( low efficiancy)
Can drugs as agonists?
- Yes
- Drugs can:
- Increase neurotransmitter synthesis or release
- Prolonging action of the neurotransmitter within the synapse
What is a synapse?
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).
What are neurotransmitters?
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.
Is **ligand-receptor binding **forever? What does it do?
- **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.
Are receptors forever?
Receptor proteins have a particular life span; the number and sensitivity of receptors can also change.
What is up-regulation?
**Up-regulation: **number of receptors increases
What is down-regulation?
**Down-regulation: **number of receptors is reduced in response to absence of ligands or chronic activation.
Are all receptors the same? why is this important?
- **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
What is a goal of neuropharmacology?
hint: involves receptors
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.
What are neurons?
- Neurons are one of the two primary cell types in the nervous system.
- Neurons transmit information through electrical signaling
What are the functions of glial cells?
- 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
What do neurons do will the information?
- Collect input
- drugs can alter or create input
- Process/decide in some way
- Produce output
How many types of neurons are there? list them:
3 main types of neurons
Sensory neurons, interneurons, and motor neurons
What are sensory neurons?
**Sensory neurons **transform stimuli outside the body into electrical signals.
What are interneurons?
-
Interneurons: neurons in brain and spinal cord that form neural circuits
- responsible for all non-sensory processing (memory, cognition, decision-making, conscious sensation)
What are motor neurons?
**Motor neurons **transfer electrical signals into muscle movement.
What are the parts of a neuron?
soma, dendrites and axon
What is the soma?
**Soma- **cell body; contains nucleus and other organelles.
What are the dendrites?
**Dendrites- **projections form the soma that receive information.
What is the axon?
Axon- extension that conducts electrical signals from the cell body to the terminal buttons.
What is convergence?
**Covergence: **information coming from a vast number of neurons all comes together into a single neuron.
What is divergence?
**Divergence: **information from one neuron may be passed on to thousands of others
How do neurons communicate?
hint: very long
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.
What is the soma #2?
Soma
- cell body
- metabolic machinery
What are the dendrites #2?
- Dendrites:
- Receive input from neurons at synapses (post synaptic)
What are axons #2?
- Axons
- Before synapse (presynaptic)
- Originates at Axon Hillock
- Often insulated with Myelin sheaths
- Ends at presynaptic terminal button
- Release neurotransmitters
What’s so imporant about the synapse?
- 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
Is the structure fixed?
- 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
What are gated channels?
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
How do ligand-gate channels work?
**Ligand-gated channel- **opens when a ligand binds to a receptor.
How do voltage-gated channel work?
Voltage-gated channel- opens when the electrical potential across the membrane is altered.
What is the importance of second-messenger systems?
Some ion channels are modified by second messengers which cause intracellular phophorylation (addition of a phosphate group) and regulate the state of the channel.
how does neuronal signaling work?
- 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
What happens to neurotransmitters?
- 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
What are the two main receptor types?
- 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
How does binding work (overview)?
- 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 ->
What is the action potential?
- 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
What is the Action potential #2?
- 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
What is the resting potentinal?
- 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?
What are neural membranes?
Lipid bylayer- will not dissolve
Barrier to ions, proteins and other molecules
Distribution of ion in and outside the cell comparison:
- Na+
- outside: 440
- inside: 50
- K+
- outside: 20
- inside: 400
- Cl-
- outside: 560
- inside: 40-150
- Ca2+
- outside: 10
- inside: .0001
What about chemical gradient?
- Chemical gradient is similar but for the particualr molecule, regardless of charge
- In other words, equilibrium for sodium, potassium, calcium, etc.
What about equilibrium both electrical and chemical?
- 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.
Synaptic Transmission
Neurotransmitters (chemical)
Cause either depolarization (excitation, EPSP) or hyperpolarization (inhibition, IPSP)
