test 1 study guide
test 1 study guide NROSCI 0081
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This 12 page Study Guide was uploaded by Anna Perry on Friday October 9, 2015. The Study Guide belongs to NROSCI 0081 at University of Pittsburgh taught by Fanselow,Erika in Fall 2015. Since its upload, it has received 21 views. For similar materials see DRUGS AND BEHAVIOR in Neuroscience at University of Pittsburgh.
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Date Created: 10/09/15
Drugs and Behavior INTRO A Drug Terminology 1 Instrumental use Drug use for a speci c purpose other than getting high 2 Recreational use Drug use to achieve some pleasurable effect 3 Drug abuse Drugtaking behavior resulting in some form of physical mental or social impairment 4 Psychoactive psychotropic drugs Drugs that affect behavior by altering the function of the central nervous system B Five Basic Principals of Psychoactive Drugs 1 Psychoactive drugs typically have as a primary molecular target a protein that performs a normal function in neurons 2 Every drug has diverse speci c and nonspeci c effects a Speci c effects are due to molecular interactions with target sites b Nonspeci c effects are due to the characteristics and current state of the individual including i Previous drugtaking experience ii Present mood iii Expectations of drug effect eg placebo 3 The magnitude quality and diversity of a drug s effects depend on the exposure amount and route 4 The effects of any psychoactive drug depends on an individual s genetics and life history including mood and exposure to other drugs 5 Exposure to a drug acute andor chronic can cause longterm neurological changes that include addiction PRINCIPLES OF DRUG ACTION A Exposure of the Brain to a Drug 1 Drugs must travel from the site of entry into the body to the brain via the circulatory system a How much drug gets to the brain and how fast it gets there depends of the ability of the drug to travel through the body and reach the brain intact 2 Pharmacokinetics is the processes involved in the movement of drugs within biological systems including absorption distribution metabolism and excretion a quotThe effect of the body on the drugsquot 3 Pharmacodynamics is the study of biochemical and physiological effects of drugs and their mechanism of acUon a quotThe effect of the drugs on the bodyquot 4 What matters is how many molecules of a drug are available to act at a given site of action a Concentration of the drug depends on i Dose administered ii Rate of accumulation iii Rate of removal from the site of action B Receptors Ligands 1 Receptor A protein located on the surface of or inside of a cell that is the site of action for a drug or other molecule eg a neurotransmitter a Receptors recognize a speci c molecular shape b Binding to a receptor is temporary c Receptor subtypes are not xed number and sensitivity can change d Receptors can have similar subtypes 2 Ligand A molecule eg drug or neurotransmitter that binds to a receptor a Ligand binding alters the shape of the receptor conformational change b Again binding to a receptor is temporary 3 There are two types ligands Agonists and Antagonist C Agonists Antagonists 1 An agonist binds to a receptor and causes the drug actioneffect 2 An antagonist binds to a receptor and prevents the binding of the agonist causing no drug actioneffect D Dose vs Dosage 1 Dose quantity of drug administered a Usually reported as amount of drug by body weight eg mgkg 2 Dosage number of administrations per unit time a eg mgkg four times a day for three days E DoseResponse Curves 1 The relationship between the dose administered and the behavioral response observed is called the dose response functioncurve a Made by making a graph indicating the size of the response to the drug for a given amount of drug administered 2 The threshold dose is the minimally effective dose 3 The maximal response is the greatest degree of a given response that can be achieved with a speci c drug 4 The therapeutic window is doses for which a given therapeutic response occurs F Therapeutic Index 1 The therapeutic index is a measure of a drug s relative safety for use computed as the ratio of LD50 t0 ED50 a b C ED50 or the Effective Dose for 50 is the dose at which half of the maximal effect is achieved OR effective dose for half of the subjects tested LD50 or the Lethal Dose for 50 is only used in animal studies TD50 or the Toxic Dose for 50 is when you start to get dangerous side effects It is used in human drug studies and the therapeutic index is found using TD5oED50 2 The greater the LD50ED50 the safer the drug optimally more than 100 less than 10 is considered very unsafe 3 The margin of safety is the difference between ED50 and TD50 G Efficacy Potency 1 Ef cacy is how well a drug can produce a given effect a b Not all drugs in a given class produce the same maximal effect efficacy To see which drug is more effective has greater efficacy on a DR curve focus on which is greater on the yaxis drug effect 2 Potency is how much of a drug is needed to produce a given effect a b C Not all drugs produce the maximal effect a the same doses potency The less of a drug required to produce an effect the greater the drug s potency To see which drug is more potent on a DR curve focus on which is smaller on the xaxis dose mg H Drug Interactions 1 The potency andor efficacy of a drug can be altered by the presence of another drug or substance Antagonism the potency or efficacy of a drug is reduced in the presence of another drug Synergism Two drugs together are more potent andor efficacious than either drug given alone Additive summation The effect of 2 drugs presented together is the sum of the effects of each individually Potentiation is when one drug has no effect on its own but increases the potency of another drug III PHARMACOKINETICS A Route of Drug Administration 1 Oral a b Selfadministered economical avoids discomfort To be effective drug must dissolve in stomach uids but not be broken down by digestive enzymes Most of the drug is absorbed through the small intestine The rate of absorption is hard to predict because it depends on the rate at which food leaves the stomach and how much food was in the stomach before Blood and any drug in the blood goes to the liver before going to the rest of the body The liver can metabolize some drug molecules which changes their properties This is rst pass metabolism 2 Intravenous IV injected directly into a vein a Most rapid and accurate route of administration because drug goes directly into blood and does not need to pass through cell membrane Rapid administration can be dangerous because it takes little time to correct an overdoes or allergic reaction 3 Intramuscular IM injected directly into muscle 4 Subcutaneous SC Injected below skin 5 Inhalation a b C Drug absorption into the blood occurs through thelungs Absorption is rapid because of the large surface area inside the lungs Effect on the brain is rapid seconds because the path from the lungs to the brain is short d Topical transdermal Direct to the brain Route of administration dictates the rate of absorption into the blood Factors include a Area of the absorbing surfaces b Number of cell membranes that must be crossed c The amount of drug broken down by stomach or liver enzymes d Presence of food B Absorption and Distribution 1 Once a drug is in the body it needs to get to its site of action such as the brain 2 Drugs are hydrophilic if they dissolve well in water and hydrophobic if they dissolve well in fats or oils 3 While neurons need nutrients in the blood if they were directly in contact with it they could be damaged seizures For this reason they are surrounded by cerebrospinal uid a Brain capillaries transfer required molecules to the CSF so neurons can use them but deleterious molecules can t get in b Brain capillaries are surrounded by astrocytes 4 The partition between the blood and CSF is the bloodbrain barrier C BindingStorage 1 Once the drug is in the CSF it binds to a molecular target or sites where no biological action occurs depot binding a Depot binding stores drug molecules in various places in the body like muscles and fat b This affects the number of drug molecules circulating in the blood which alters the effects of the drug D Inactivation Metabolism of Drugs 1 Most drug molecules are altered by metabolic enzymes in the liver or digestive enzymes in the stomach a Once they are broken down they turn into molecules called metabolites which are usuaHyinache 2 Enzyme induction use of a drug can cause the body to make more of an enzyme which increases the breakdown of that drug as well as other drugs affected by the same enzyme ooim a Contributes to tolerance 3 Enzyme inhibition some drugs can reduce the action of enzymes which increases the amount of the drug and others this makes the effects of the administered drug more intense and it lasts longer E ExcretionElimination 1 Most elimination of drugs and metabolites occurs via the kidneys 2 Halflife is the term used to say how long it takes for the body to get rid of half of the drug circulating in the blood a Two halflives would get the concentration down to 14 IV NEUROANATOMY A Divisions of the Nervous System 1 The nervous system has one main function to keep you alive lts three tasks are a Gather information from the environment and send it to the brain so it knows what is there sensory part of the PNS b Decide what to do by using sensory info and previous experience neurons in CNS c Do it motor part of PNS B The Central Nervous System CNS is the brain and spinal cord 1 Afferent nerves carry sensory info to the spinal cord which transmits this input to the brain 2 Efferent neurons that control muscles go from the brain through the spinal cord to the muscles C The Peripheral Nervous System PNS is everything outside the skull and spine 1 Somatic PNS is voluntary a Transmits sensory information b Produces movement c Contains nerves to and from muscles joints skin d Receives sensory information via afferent sensory neurons e Sends commands to muscles via efferent motor neurons 2 Autonomic PNS is re exes a Controls involuntary musclesbody function b Helps body either provide or conserve energy 3 Divisions of Autonomic PNS a The sympathetic PNS arouses the body for action and mediates the quotfight or ightquot response i Dilates pupils ii Accelerates heartbeat iii Constricts blood vessels in skin b The parasympathetic PNS prepares the body to quotrest and digestquot i Constrict pupils ii Slows heartbeat iii Dilates blood vessels in skin 4 Both divisions of the PNS contain two types of nerves a Afferent brings signals to the CNS arrives b Efferent sends signals from the CNS exits D Divisions of the brain 1 Hindbrain a Medulla controls breathing heart rate digestion blood pressure b Cerebellum Controls complex movements such as coordination and balance c Pons Neuronal connections between the cerebellum and the cerebral cortex d Reticular formation Regulates sleep vs waking 2 Midbrain a Tectum controls sensory and motor re exes b Tegmentum neurons involved in movement drug addiction schizophrenia 3 Forebrain a Basal Ganglia involved in initiation and control of movement affected in parkinson s i Circuit involving the basal ganglia uses dopamine b Limbic system Three divisions i Hippocampus involved in memory and learning ii Amygdala involved in emotional responses fear conditioning iii Cingulate cortex Emotional component of pain and anticipation of pain c Neocortex The outer part of the brain divided into four lobes i Occipital vision ii Parietal touch perception of the body iii Temporal hearing learning memory emotion iv Frontal control of movement planning and directing behavior E Parts of Neurons 1 2 Soma Cell body Myelin insulates some neurons and increases the speed at which they propagate a Reduces the amount of ions that leak out of the axon as the action potential moves along it b Loss of myelin is Multiple Sclerosis Axon transmits signal from soma to terminal boutons Dendrites receive input from other neurons and send that input to the soma Direction neuronal signals travel a Dendrites gt soma gt axon gt terminal boutons F Types of Glia glue 1 2 3 Astrocytes provide structural support for neurons maintain the right amounts of ions in the CSF and contribute to the bloodbrain barrier Oligodendrocytes Form myelin around axons in the CNS Schwann cells Form myelin around axons in the PNS V NEUROPHYSIOLOGY A Cell membrane and ions 1 2 3 4 The concentration of K is higher inside the cell The concentration of Na is lower inside the cell The concentration of Cl is lower inside the cell The inside has a net negative charge relative to the outside giving it a negative membrane potential B Neurotransmitter receptors 1 JUN Neurotransmitter receptors are embedded in cell membranes and contain channels through which ions can cross Selectivity receptors only open for certain ions Gating receptors only open when triggered to do so a Ligandgated when a ligand binds to this type of receptor the binding causes a conformational change in the receptor molecule which either opens or closes the channel b Voltagegated when there is a change in the relative charge across the cell membrane this causes a conformational change in the receptor 4 molecule which either opens or closes the channel The difference of charged ions on different sides of the membrane creates a voltage across the cell membrane this is membrane potential C Two things maintain the neuronal ion concentration gradients 1 2 The NalK pump uses ATP to move 3 Na ions out of the neuron for every 2 K it brings in The net negative charge inside a neuron tends to pull positive ions in and push negative ones out electrostatic force D lons crossing affect membrane potential 1 First ligandgated channels open depolarizing the membrane As the membrane depolarizes voltage gated Na channels open letting Na into the membrane which further depolarizes the membrane Voltagegated K channels then open and K leaves the neuron which hyperpolarizes it Also Na channels inactivate close so Na ow stops causing membrane to repolarize negative feedback loop When K channels open K ions leave the cell making it more negatively charged hyperpolarized When Na channels open Na ions enter the cell making it more positively charged depolarized positive feedback loop When Cl channels open Cl ions enter the cell making it more negatively charged hyperpolarized Resting membrane potential is when a neuron is neither sending nor receiving a signal 70 mV Action potential threshold unconstrained Na channel opening causes the membrane potential to depolarize rapidly Action potential undershoot this occurs because K channels inactivate slowly allowing K to continue to exit the neuron This pulls the membrane potential below the resting potential a Relative refractory period the stillopen K channels make it more difficult to start a second action potential too close in time to the rst because its starting from a lower voltage b Absolute refractory period inactivated Na channels prevent another action potential from starting it can t get another action potential during that time 8 Polarization is a separation of charge think negativity 9 Hyperpolarization when the membrane potential becomes more negative 10 Depolarization when the membrane potential becomes more positive 11 goom Feedback loop of propagation Action potential depolarizes the axon Depolarization opens nearby Na channels Na enters cell Depolarization opens nearby Na channels VI NEUROTRANSMISSION A Synapses 1 The synaptic cleft is the space between the membranes of the pre and postsynaptic neurons a b C Axodendritic Axon gt dendrite tiny vote about what the neuron does Axosomatic axon gt soma more impact bc directly to soma Tends to be inhibitory Axoaxonic axon gt axon interception 2 Vesicles have uid on their inside and can contain molecules such as neurotransmitters a Gather on the presynaptic side of synaptic cleft 3 Vesicle fusion causes exocytosis a b A vesicle containing neurotransmitter is near membrane A group of molecules hold the vesicle right up next to the membrane and prime it to fuse When an action potential depolarizes the presynaptic membrane this opens voltage gated Ca2 channels The Ca2 ions bind to the molecules holding the vesicle to the membrane and trigger fusion Fusing with the membrane causes the neurotransmitter to be released exocytosis Once the vesicle has released its neurotransmitter it is brought up into the neuron again endocytosis i The lipid bilayer is recycled and a new vesicle forms B Neurotransmitter In The Synaptic Cleft 1 The newlyreleased neurotransmitter molecules are close to the postsynaptic receptors and can bind to them 2 Neurotransmitters don t go into postsynaptic cell 3 a They bind to receptors in the cell membrane and open them for other things to go in Hgand If neurotransmitters stayed in the synaptic cleft a The postsynaptic cell would respond inde nitely to the signal from the presynaptic neuron b There would be no way to send a second separate signal it would merge with the rst 4 3 Methods by which neurotransmitters can be cleared from the synaptic cleft a Degradation broken down by enzymes b Reuptake brought back into the presynaptic neuron via transporters in the cell membrane c Uptake by glial cells brought into surrounding glial cells via transporters C Neuromodulators 1 2 3 Molecules released by neurons that bind to receptors on neurons other than the one directly postsynaptic Tend to regulate neuronal activity over larger regions and on a slower time scale than neurotransmitters Some molecules can act as both neurotransmitters and neuromodulators depending on where the receptors are that they activate D Neurotransmitter Receptors 1 2 3 Receptors are made of groups of proteins each of which is a subunit lonotropic receptors directly open ion channels but are not voltagegated or Metabotropic receptors indirectly affect processes inside the cell and have two routes of action a Direct action of Gprotein b Indirect action via second messenger E Neurotransmitter Synthesis 1 Synthesis building blocks of a transmitter substance are imported into the terminal where the neurotransmitter is synthesized and packaged into vesicles Derived at two locations in the cell a Axon Terminal building blocks from food are pumped into cell via transporters b Cell body proteins made via DNA are transported to the synaptic terminal Enzymes can convert precursor molecules into neurotransmitters VII NEUROTRANSMI39ITERS A What Do Receptors Affected Do 1 Excitation of a neuron increases the likelihood that the postsynaptic neuron will initiate an action potential at the soma EPSPs excitatory post synaptic potential a Excitatory neurotransmitters bind to receptors opening ligandgated Na channels producing EPSPs in postsynaptic neuron gt triggers action potential 2 Inhibition of a neuron decreases the same IPSPs inhibitory postsynaptic potential a Inhibitory neurotransmitters bind to receptors opening ligandgated K or Cl channels producing IPSPs in postsynaptic neuron
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