Assignment 3: Drugs Change Our Behavior Via Actions on Neurons.

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1 Assignment 3: Drugs Change Our Behavior Via Actions on Neurons. In order for us to be able to understand how drugs and diseases affect the brain and our behavior we need to have a basic understanding of how neurons work. To achieve this goal we will use an analysis of the changes produced by addictive drugs to illustrate the key concepts in chemical neurotransmission. Chemical neurotransmission is the process by which neurons produce our thoughts, feelings and behavior. Preparation. Read chapter 3 and complete the reading quiz on D2L before you complete this assignment. You will need to have your book open. Your book will directly connect you to a web site to access video cases for this assignment so you must have access to an internet connection but all other browsers and Skype should be off while you complete the assignment. Course Note: In the traditional lecture we use two 50-minute lectures to work through these concepts. Allow 100 minutes to complete this assignment. Don t forget that you can use the Live Online Chat or Discussion Board for this unit to ask questions about the assignment. GRADING: This assignment is worth 45 points. When you have completed the exercises in this handout you will be required to enter your answers in D2L. You will be allowed to complete the assignment up to two times. D2L will grade your assignment you will be able to view all incorrect answers under submissions. Please keep in mind that once you start an assignment on D2L you must finish it within the time limit. So do not proceed to D2L until you have completed all parts of the assignment in this handout first. Part 1. Neurotransmission Lets review the key concepts from the assigned reading. Select the Assignments Menu in your book and then Assignment 3. Click on the Neurotransmission video. 1.) When acetylcholine binds to its receptor what happens? a.) A change in the charge of the neuron occurs producing an EPSP. b.) Sodium ions enter the neuron. c.) The fist step in neurotransmission (Input) is initiated. d.) all of these.

2 Effects of Acetylcholine on Behavior Acetylcholine is a neurotransmitter that is used at the neuromuscular junction to regulate the movement of muscles in the peripheral nervous system and in the arousal, attention, motivation, motor, sensory and emotional pathways in the central nervous system (brain and spinal cord). What kind of Neurotransmitter is Acetylcholine? Let s find out! 1) Select Model Neuron from the Experiments menu in your book. The cursor is currently in the sodium (Na+) box- type in 1 before the zero (to = 10). Entering a number in this box simulates the influx of sodium into the neuron (i.e. the INPUT step in chemical neurotransmission). Repeat. But this time use two hands and type in 1 and then hit control W (Windows) or command W (Mac OS). This stops the sim and will allow you to make observations. To reactivate it just type control G (Windows) or command G (MacOS). Note: you can change the speed of the sim by using the popup menu in the lower left-hand corner of the sim window. You should have obtained an EPSP that looks like this: Take your mouse pointer and put the tip on the peak point of the EPSP. It should read about -60 mv. Now place the mouse pointer tip on the flat line (resting membrane potential or RMP) on either side of the EPSP and you should get a reading of -70 mv. [Note: if your mouse seems to move too fast just turn down the sensitivity in your preferences file for your operating system]. But what s the point? Let us assume that we are looking at a motor neuron that releases acetylcholine to make a muscle contract to move your arm. You should recall from your reading that a neuron must produce an action potential in order to release its neurotransmitter (i.e., to move your arm).

3 But to produce an action potential the resting membrane potential must be driven (depolarized) from its starting point when inactive (-70 mv in this case) to the neuron s absolute threshold which is a value more positive in charge than the resting membrane potential (specific to each neuron but an average around -40 mv). If this happens voltage gated sodium channels (set to open at the absolute threshold) all open simultaneously on the axon hillock flooding the neuron with positively charged sodium ions (Na+) and an action potential is produced. 2.) an influx of sodium ions a.) is inhibitory or hyperpolarizes a neuron b.) is excitatory or depolarizes a neuron c.) is neurotoxic d.) has no effect on a neuron (circle your answer here you will need it to complete the assignment on D2L). 3.) the absolute threshold a.) is produced when sodium ions leave the neuron b.) is the value of the neuron at rest c.) is the voltage necessary to open voltage gated sodium channels at the axon hillock to trigger an action potential. d.) is a bogus term you made up (circle your answer here you will need it to complete the assignment on D2L). If you have not already done so restart the sim (control/command G) 4.) What happens to potassium (K+) when sodium enters the cell? If necessary go back and enter different amounts of sodium in the sodium box and watch what happens to the K+ ions. What happened? a.) K+ levels inside the neuron rose. b.) K+ levels inside the cell remained unchanged. c.) K+ levels inside the neuron dropped as sodium ions entered the cell. d.) none of these If you have not already done so restart the sim (control/command G) and then go to the Neurotransmitter menu and select Acetylcholine. A button and slider bar will appear at the bottom of the sim window. Click on this new Acetylcholine button. Repeat this process but watch what happens to the current and also watch the sodium ion indicators in the upper left hand corner of your window. You should have obtained a small EPSP and noticed that acetylcholine allows sodium into the neuron by acting on ionotopic receptors usually located

4 on dendrites. The acetylcholine receptor is an example of an excitatory ionotropic receptor. It is a good example of the INPUT step 1 in chemical neurotransmission. To see a diagram comparing ionotropic receptors select Ionotropic receptor from the Neurons menu in the sim. If you do not understand this process, then repeat the sim again until you prove to yourself that this is what happens. Step 2 (Trigger). In the next part of this assignment we will illustrate how the INPUT step leads to the Trigger step (generation of an action potential) in chemical neurotransmission. Now gradually increase the amount of acetylcholine applied to the receptors by moving the slider (located next to the acetylcholine button) to the right (be sure to click the button each time you increase the amount) until you trigger an action potential. Action Potential The Action Potential shown above is from a hippocampal pyramidal neuron. It should be very similar to the simulated action potential that you produced in your sim. Remember that if a neuron produces an action potential it will release its neurotransmitter and produce a change in behavior. Summary: If enough sodium enters the neuron through acetylcholine receptors and the EPSP reaches the absolute threshold then an action potential is produce at the axon hillock and our behavior and thoughts change. 5.) What kind of Neurotransmitter is Acetylcholine? a.) inhibitory b.) excitatory c.) hormone d.) neuromodulator e.) neuroactive substance GABA and glutamate are important neurotransmitters and both will play a major role in our discussion of disorders later in this course. For now, your mission

5 is to find out how they work at the input step of neurotransmission and their likely effect on behavior. Follow the steps below for each and then fill in the information in Table 1 (you will need this information to answer question 6 assignment on D2L). Repeat these Steps for each Neurotransmitter 1.) Make sure the Drugs Menu is set to NONE 2.) Select GABA or Glutamate from the Neurotransmitter menu and click on the new button that appears at the bottom of the sim. Start with a low amount and then gradually increase the amount with the slider. Each time you increase the amount click on the button to see what happens. Be sure to watch the current and the flow of ions (sliders in the upper left hand corner of the sim window). This is the same process you completed for evaluating acetylcholine. 3.) Fill in your information in Table 1. Table 1. Used to complete Question 6 on D2L Neurotransmitter GABA Glutamate Current produced IPSP or EPSP? Ion influx (Na +,Ca 2+, K +,Cl - ) Will this neurotransmitter stimulate behavior or inhibit behavior? Important Technical Note: Neurotransmitters often have multiple receptors. The sim used in this assignment uses the following ionotropic receptors: the GABA- A receptor to test the effects of GABA. the AMPA receptor to test the effects of Glutamate. the nicotinic receptor to test the effects of acetylcholine. Step 3 (Propagation). Once generated at the axon hillock it is then rapidly propagated down the axon as the action potential conducts along the axon it simply opens more voltage gated sodium and potassium channels essentially creating a new action potential at each point in unmyelinated axons. In myelinated axons the voltage gated channels are only present at the gaps between myelin segments called the nodes of Ranvier. In the video Neurotransmission it only looks like the action potential is moving due to its speed. In reality the action potential is jumping (latin: saltare) from one node to the next in a process called saltatory conduction. Because myelinated axons use salutatory conduction they fire many times faster than unmyelinated axons due to the fact that they use fewer ion channels (which require time to open and close). Because they use fewer ion channels they do not need as many of the

6 pumps (sodium-potassium pumps) to restore the resting membrane potential. Pumps require energy which means less glucose is needed. To put this savings in perspective consider that in your brain 90% of the synapses involve myelinated neurons. Your mostly myelinated brain weighs about 1% of your body weight but it uses 10-15% of the glucose that you take in! Imagine what your eating patterns would be like if this ratio was reversed. A final advantage of myelinated axons is the ability to pack more neurons into a smaller space (if you have two uninsulated electrical wires touching they short out the same is true for two touching unmeylinated axons). So if you want to know what a human would look like behaviorally if we had a brain of mostly unmyelinated axons imagine an earthworm. Moving slow and not particularly sophisticated in its behavior. The earthworm has a nervous system of 305 mostly unmyelinated axons (by comparison we have three million myelinated axons in just the hippocampus). 7.) What are the advantages of myelinated axons over unmyelinated axons for the human brain? a.) you can have more neurons in a smaller space b.) we can think faster c.) we need to eat much less d.) behavior can be more sophisticated e.) all of these are advantages Step 4 (Output). When the action potential reaches the nerve ending it opens ion channels that are selective for calcium. Calcium activates a series of enzymes (e.g., the synapsins) that cause containers of neurotransmitter (called synaptic vesicles) to fuse with the presynaptic membrane and then expel their chemicals into the synapase via exocytosis. Step 5 (Termination). There were three mechanisms for removing neurotransmitter from the synapse discussed in the video. 8.) Which method is used to remove acetylcholine from the synapse? a.) reuptake b.) glial cell absorption c.) enzyme degradation d.) the method used depended on the location of the synapse in the brain Part 2. Drugs, Behavior and Addiction To help you better understand how drugs affect your behavior you are going to look at the effects of three drugs and determine based on how they effect neurons whether the drug is an agonist or antagonist and whether the

7 drug is a stimulant or depressant. In chapter 3 you learned that agonists enhance the actions of naturally occurring chemicals (such as neurotransmitters) and that antagonists block the actions of neurotransmitters preventing them from affecting behavior. This method of classification is based on how the drug binds to its target receptor. Drugs are also classified based on their psychotropic effects (effects on the mind and behavior). So a drug that shuts the brain down by blocking excitation or increasing inhibition and slows or inhibits behavior is defined as a CNS depressant. A psychostimulant will increase motor function, speed of processing and decrease sleep. These drugs usually block inhibitory receptors or act as agonists at receptors for excitatory neurotransmitters. Repeat these Steps for each Drug 1.) Select GABA or Glutamate from the Neurotransmitter menu as indicated in Table 2 and click on the new button that appears at the bottom of the sim. IMPORTANT: Start with the slider set to highest amount of neurotransmitter release and click on the neurotransmitter button to see what happens. Be sure to watch the current and the flow of ions (sliders in the upper left hand corner of the sim window). This is the same process you completed for evaluating these neurotransmitters in Part 1. Make sure the Drugs Menu is set to none each time you change neurotransmitters. 2.) Select the drug indicated in column 2 (Table 2) and click on the Drug or neurotransmitter button that appears at the bottom of the sim window (either button tests the effects of both compounds together). Start with a low amount and then gradually increase the amount with the slider. Each time you increase the amount click on the button to see what happens. You can also change the amount of neurotransmitter. Be sure to watch the current and the flow of ions (sliders in the upper left hand corner of the sim window). Keep changing the amounts until you are convinced you know how it works. 3.) Fill in your information in Table 2. Table 2. Used to complete Question 9 on D2L Set the Neurotransmitter to GABA Set the Drug To Barbiturates Current produced IPSP, EPSP or Action potential or flat line (RMP)? Is this drug a stimulant or depressant? Glutamate Phencyclidine* RMP=resting membrane potential *Is also known as PCP or angel dust. PCP also produces hallucinations and is given a second classification as an hallucinogen or psychedelic.

8 Addiction The barbiturates are very addictive and chemical dependence develops rapidly while phencyclidine (or PCP) is not particularly addictive and rarely leads to dependence. Lets now take a look and see what factors determine whether a drug will be addictive. Select the Assignments Menu in your book and then Assignment 3. Click on the Addiction video. Be sure to take good notes. You may either answer the questions below as you go along or at the end. 10.) According to Leshner addiction a.) is voluntary behavior b.) is defined as a lot of drug taking behavior c.) is a chronic relapsing disease characterized by a different state of mind d.) is special type of personality disorder usually preceded by child abuse 11.) Addictive drugs bombard the brain with unusually high levels of or agonists that stimulate the pleasure centers of the brain. a.) dopamine b.) GABA c.) Glutamate d.) Acetylcholine 12.) Drugs that are addictive tend to produce pleasure very quickly (within a few minutes) In a cocaine user, how fast does cocaine start to produce pleasure? a.) within 3-4 minutes b.) in 10 minutes c.) in minutes d.) in 60 minutes 13.) Drugs that are addictive must also induce tolerance. Which of the following statements from the addicts interviewed indicates that they have developed tolerance? a.) My personality changed.i didn t feel the same. b.) I am always trying to get back to that first time. c.) I have been trying for 30 years to get back to the first time. d.) all of these

9 14.) Neuronal tolerance occurs in the brain when neurons decrease the number of receptors targeted by the drug causing the addict to take more of the drug to produce the same behavioral effect. Based on the glucose scans (from the cocaine addict) shown in the video how long after a person stops taking cocaine does it take for the brain to return to normal? a.) within a few minutes b.) within a few hours c.) within 10 days d.) at least 100 days with the upper limit unknown 15.) Drugs that are addictive must also induce withdrawal symptoms. In a cocaine user, how fast does cocaine start to produce severe CNS depression causing the addict to want to use again (base your conclusion off of the PET scans and the addicts personal descriptions)? a.) within 3-4 minutes b.) at about 10 minutes c.) by 20 minutes d.) after 60 minutes 16.) Drugs that dramatically raise dopamine levels in the brain not only affect the pleasure or reward pathways but also other pathways in the brain that use dopamine. Each of the following symptoms listed below are produced by changes in dopamine pathways. Which of the following behaviors was/were also reported by the addicts interviewed in the video? a.) paranoia b.) aggression c.) delusions d.) hallucinations e.) all of these 17.) What are the barriers identified in the film that currently prevent the adequate treatment of drug addicts? Select ALL that apply. a.) the general public views addicts as criminals to be punished not treated b.) addicts do not understand why they can t stop on their own c.) shame d.) the changes in the brain may last a lifetime e.) addicts often do not have the appropriate social skills f.) addicts often do not have the training or education to obtain employment to afford treatment or stay clean g.) addicts tend to be isolated but support groups are needed for successful recovery h.) the addict mind wants quick reward but recovery is slow and lasts a lifetime

10 The Special Case of Nicotine Nicotine is the active drug in cigarettes and many people find it very difficult to quit smoking. Based on our discussion on addiction we should expect that nicotine produces direct effects on dopamine release but nicotine targets a special type of receptor for acetylcholine called the nicotinic receptor. Think about why people smoke. You can probably think of people who smoke to relax and others who smoke for stimulant effects. So how can nicotine produce this very odd set of effects? Lets find out. 1.) Select Model Neuron from the Experiments menu in your book. 2.) Select Acetylcholine from the Neurotansmitter menu and make sure that the amount of chemical is set to about 25% on the slider bar. Just so that you get a small EPSP. Make sure drugs is set to none. 3.) Click on the Acetylcholine button. Did you get a small EPSP? 4.) Now select Nicotine from the drugs menu. Click on the Nicotine button ONLY ONCE. And write down what happened? 18.) Based on this first observation nicotine is (circle one) a.) An acetylcholine agonist and psychostimulant b.) An acetylcholine antagonist and psychostimulant c.) An acetylcholine agonist and CNS depressant d.) An acetylcholine antagonist and CNS depressant 5.) Now click on the Nicotine button again (you can now use the button as many times as you want). Now what happened? 19.) Based on this second observation nicotine is (circle one) a.) An acetylcholine agonist and psychostimulant b.) An acetylcholine antagonist and psychostimulant c.) An acetylcholine agonist and CNS depressant d.) An acetylcholine antagonist and CNS depressant Did you do break the computer? No. The effect you are getting is real. If you want to find out what s going on, then bring this up in the next live chat (not the discussion boards). You are now ready to complete the online questions for this assignment. Remember you only are allowed up to two attempts so if you do not feel ready go back and do the assignment over. It is your last score that counts. You will need this handout. Close your book and use the Respondus Browser to enter your answers in D2L (Assignment 3).