exam 3 study guide
exam 3 study guide NROSCI 0081
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This 20 page Study Guide was uploaded by Anna Perry on Sunday December 6, 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 17 views. For similar materials see DRUGS AND BEHAVIOR in Neuroscience at University of Pittsburgh.
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Date Created: 12/06/15
I. Pain/Opioids A. Analgesia is the relief from pain 1. Analgesic = painkiller B. Opioids/Opiates 1. Opioids are all substances that bind to opioid receptors, including endogenous, synthetically, and naturally derived substances a. Opioid receptors were identified first, then substances were identified in the brain that were able to bind to receptors (endogenous opioids) i. Endorphins, enkephalins, dynorphins, emdomorphins b. These chemicals were shown to produce an analgesic effect c. They are also involved in reward, feeding, and stress response d. There are 3 main types of receptor subtypes: μ (mu) δ (delta) and κ (kappa) i. Each have unique distributions throughout the nervous system ii. Each bind to different endogenous opioids and therefore have different functions iii. Most opioid analgesic drugs bind to the μ receptor, which is distributed throughout the brain and spinal chord. 2. Opiates are substances naturally derived from opium poppy C. Types 1. Morphine: refined active ingredient of opium poppy a. Slight modification yields Codeine: less analgesic effect, but fewer side effects 2. Heroin: more lipid soluble than morphine (crosses BBB easily) 3. Fentanyl: 80xs more potent than morphine, mostly used for anesthesia and neuropathic pain D. Pharmacokinetics 1. Most opioids do not easily cross the BBB (heroin is an exception) 2. They distribute evenly throughout the body, including across the placenta E. Effects 1. Physiological and Behavioral a. At low doses: pain relief, slight respiratory depression, pupils constrict, drowsiness, decreased sensitivity to environment, impaired ability to concentrate b. At higher doses (inhaled or injected): elation or euphoria, nausea, vomiting c. At even higher doses: unconsciousness, blood pressure and body temperature fall, pupils very constricted 2. Side Effects a. Mixing opiates with alcohol can be detrimental, due to respiratory depression 3. Neurochemical Effects of Opioid Receptor Activation a. Opioid receptors are metabotropic (G-protein coupled) i. Can open ion channels ii. Can cause second-messenger effects inside a neuron b. Overall effects are inhibitory onto downstream targets c. Postsynaptic inhibition i. Opioid receptors open K+ channels, which hyperpolarizes the downstream cell ii. Causes an IPSP d. Axoaxonic inhibition i. Opioids can close Ca2+ channels, reducing neurotransmitter release ii. Reducing release of dopamine, norepinephrine, and GABA F. Tolerance 1. Continued opiate use results in tolerance of many effects of opiates a. Metabolic: increase in liver enzymes b. Pharmacodynamic: receptor desensitization, downregulation c. Behavioral tolerance 2. Euphoric properties of opiates show the fastest tolerance 3. Some effects (constipation, pupil constriction) show little or no tolerance G. Methadone is used to relieve moderate to severe pain. It is also used to prevent withdrawal symptoms II. Naloxone Therapy A. Basics 1. Naloxone is a drug capable of reversing an opioid related overdose by acting as an “opioid antagonist” a. Only works on opioid receptors b. Type of harm reduction 2. An opioid overdose occurs when the opioid receptors in the brain become oversaturated a. These receptors stimulate pleasure and facilitate breathing b. It can take up to hours after administration for opioids to interfere with breathing enough to cause death 3. Signs of overdose: unable to talk, blue/black fingernails and lips, blueish/purple or grayish skin tone, slowed breathing and pulse, unconsciousness, lack of responsiveness to outside stimuli 4. Overdose can reoccur depending on: a. Amount and half life of initial drug b. Function of liver c. Second drug usage III. Inhalants, GHB, Rohypnol A. Inhalants 1. Routes of administration a. Effects of inhaling are felt in minutes b. Mechanisms for psychotropic effects aren’t well understood 2. Behavioral Effects a. Moderate exposure: comparable to alcohol intoxication b. Heavier exposure: stronger depressant effects c. Very high exposure: anesthesia, loss of consciousness and coma 3. Pharmacokinetics/dynamics a. Rapidly absorbed from lungs into the bloodstream b. High lipid-solubility (cross BBB easily) c. Depressant effects are due to enhancement of GABA-A receptors, inhibition of NMDA glutamate receptors and inhibition of nicotinic acetylcholine receptors 4. Health Risks a. Damage to heart, liver, kidneys, lungs, bone b. Due to the high degree of lipid solubility, inhalant molecules can accumulate in the brain, especially in myelin c. Can damage myelinated nerves in the brain and in the periphery d. Very dangerous when combined with anything that causes sleepiness 5. Why are inhalants and other CNS depressants so dangerous? a. A relatively small group of cells in the medulla control breathing b. If the activity of these neurons decreases, breathing will slow until the body doesn’t get sufficient oxygen to stay alive c. The effects of multiple depressants can add up to cause breathing to stop before any individual drug would 6. Inhaled anesthetics a. Unknown why they work, especially why they suppress consciousness – they suppress effects of GABA b. Low margin of safety between anesthesia and death c. Nitrous oxide is probably the safest of inhalants because it doesn’t affect breathing B. GHB 1. Basics a. Colorless and odorless b. Is intoxicating and can be heavily sedating c. Designated as a DEA Schedule 1 drug 2. Administration a. Drank and easily absorbed into bloodstream through GI tract b. Crosses BBB easily c. Compounds that are precursors to GHB can be taken so the brain will produce more GHB than normal, leading to a GHB high 3. Behavioral Effects a. Overdose: memory impairment, depressed respiration, decreased heart rate, coma, non- convulsive seizures b. Higher overdose risk if combined with alcohol or another CNS depressant 4. Pharmacodynamics a. The GHB molecule is similar to GABA and is produced in small amounts in the brain as a metabolite of GABA i. May function as a neurotransmitter/modulator b. Agonist of some GABA-A receptors 5. Often withdrawal cannot be accomplished without medical help 6. Medical Uses for GHB a. Can be used to treat narcolepsy b. Treatment for alcohol C. Rohypnol 1. Basics a. Rohypnol is a benzodiazepine (CNS depressant) b. Used legally as a sleep-inducing drug in Europe and Mexico (illegal in the US) c. Can also cause anterograde amnesia (lack of memory for events that occur while under influence) IV. Anxiety Disorders A. Terms 1. Prevalence: the proportion of a population found to have a given condition a. Calculated by comparing the number of people with a condition with the number of people studied 2. Lifetime prevalence: the proportion of a population that have experienced a condition at some point in their life 3. Incidence: Number of new cases in a population over a given period B. Symptoms 1. Activation of the sympathetic autonomic nervous system a. Increased heart rate, sweating, shortness of breath b. The fight-or-flight mode can work for short- term emergencies, but it becomes detrimental if it lasts too long or occurs too frequently C. Generalized Anxiety Disorder (GAD) 1. Constant worry, continuously predicting, anticipating, and/or imagining dreadful events 2. Genetic contribution: GAD can run in families, but not a strong influence 3. GAD is correlated with the following changes in the brain: a. Increased size of the amygdala b. More neuronal activity in the amygdala when people with GAD are shown things that evoke negative emotions c. Reduction in GABA in multiple areas of the brain involved in fear d. GAD symptoms can be reduced by drugs that enhance GABA function (e.g. benzos) D. Panic Attacks 1. When the physiological reactions to immediate danger or anticipation of danger occur in the absence of danger, this can result in a panic attack 2. Symptoms a. Sudden, intense fearfulness b. Strong activation of the sympathetic autonomic nervous system 3. Symptoms can occur: a. In response to a particular cue in the environment b. Completely unexpectedly and without warning c. In a situation where a previous panic attack occurred 4. Panic Disorder a. Involves both panic attacks and anticipatory anxiety about potentially having a panic attack in a place that is not safe, where it would be embarrassing or where it would be impossible to escape E. Phobias 1. A phobia is a fear of something that an individual recognizes to be irrational 2. Problems with phobias can often be treated with behavioral desensitization F. Social Anxiety Disorder 1. Social anxiety disorder is an extreme fear of being evaluated or criticized by others a. Individuals with this disorder avoid most interpersonal situations or have extreme anxiety if they cannot avoid them b. Can restrict activities 2. Social anxiety disorder is correlated with the following changes in the brain: a. Levels of neuronal activity in the amygdala correlate with symptom severity G. Post-traumatic Stress Disorder 1. Can develop in response to highly-traumatic events 2. Symptoms: a. Nightmares, flashbacks, outbursts of irritability, numbing of emotional responses, lack of interest in life activities 3. There is a correlation between people who develop PTSD and a family history of psychopathology (including anxiety and depression). H. Obsessive-Compulsive Disorder 1. Obsessions: recurring, persistent, intrusive, troublesome thoughts a. These thoughts can include topics such as contamination, violence, sex, religion 2. Compulsions: repetitive rituals that are attempts to relieve the anxiety caused by the obsessive thoughts a. A sufferer is convinced that unless the compulsive behavior is completed, there will be disastrous consequences 3. OCD is correlated with the following changes in the brain: a. Increased neuronal activity in the basal ganglia when a sufferer is presented with things they fear b. The circuit involving the basal ganglia uses dopamine c. The basal ganglia is involved in initiation and control of movement 4. One theory: OCD is caused by uncontrolled movement disorder a. OCD often involves repetitive actions of “natural” behaviors that may be “weird” to the brain V. Anxiolytics A. Anxiolytics are CNS depressants – decrease neuron excitability 1. Can cause coma and death 2. Can be fatal even therapeutic doses if combined with other drugs B. Pharmacokinetics 1. Barbiturates and benzodiazepines both have binding sites on GABA, receptors and enhance the inhibitory effects of GABA a. GABA rAceptors are ionotropic Cl- channels b. Barbiturates enhance the effect of GABA by: i. Increasing the duration of GABA A receptor channel opening when GABA binds ii. Directly opening the GABA reAeptor c. Benzos enhance the effect of GABA by: i. Increasing the affinity of GABA for the GABA rAceptors, making it easier for GABA to open the receptor ii. This increases the number of times a receptor will open when GABA is bound to it 2. They do not bind at the same place on the receptor as GABA itself 3. GABA is still needed to open the channel the GABA A receptor but the effects of a given amount of GABA released at a synapse will be enhanced in the presence of anxiolytics. a. The size of the IPSP is increased in the presence of an anxiolytic C. Therapeutic Effects of Barbiturates 1. Ultrashort-acting: highly lipid-soluble a. Rapidly induce sleep (in seconds if administered IV) b. Consciousness returns in 20-30 min because drug goes into drug depots in fat and muscle and is then not in the bloodstream 2. Short/intermediate-acting a. Produce relaxation and sleep in 20-40 min, effects last 5-8 hours b. Termination of effects depends on metabolism in the liver 3. Long-acting: Poor lipid solubility a. Onset in ~1+ hour b. Effects last 10-12 hours, can be ideal for treating seizures D. Side Effects of Barbiturates 1. Can induce sleep, but sleep is abnormal 2. Cognitive and physical side effects, including mental clouding, loss of judgment, slowed reflexes 3. At high doses: staggering, jumbled speech, impaired thinking 4. At 10-20x the therapeutic dose, coma and death 5. Dangerous when combined with alcohol E. Pharmacokinetics of Barbiturates 1. Barbiturates have metabolic and pharmacodynamic tolerances 2. Mood changes and sedation show tolerance, but the lethal respiratory-depressant action of the drug doesn’t show tolerance 3. No drug can be used to reverse a barbiturate overdose 4. Withdrawal can cause a potentially-fatal rebound neuronal excitability because receptors the drug binds to are suddenly deprived of the drug F. Benzos have a lower incidence of tolerance and less severe withdrawal symptoms than barbiturates 1. Very safe therapeutic index 2. Tolerance to anti-anxiety effects rately occurs G. Therapeutic Effects of Benzos 1. Reduce sense of worry and fearfulness, and physical symptoms of anxiety 2. Less mental clouding, loss of judgment and motor coordination than with barbiturates 3. Can be used to prevent the potentially lethal withdrawal from other CNS depressants (barbiturates and alcohol) H. Pharmacokinetics of Benzos 1. Time to effect onset depends on lipid solubility 2. Duration of effects depends on metabolic rates and distribution of drug to muscle and fat 3. Benzos don’t increase liver enzymes, so metabolic tolerance doesn’t occur I. Advantages of Benzos over Barbiturates 1. High therapeutic index since benzos don’t affect the respiratory center in the medulla a. This is because GABA rAceptors on neurons that control respiration and other critical functions don’t have benzo binding sites 2. Lethal overdose is rare unless used with other depressants 3. There’s an antagonist drug that can be used to reverse effects VI. Affective Disorders A. Affective disorders are characterized by extreme positive and/or negative moods B. Major depression: recurrent episodes of negative mood, negative thoughts, and related physical symptoms 1. Characteristics of Major Depression a. Women are at a greater risk than men b. Often comorbid with other conditions, such as anxiety and/or alcohol abuse 2. Symptoms of Major Depression a. Feeling down and listless, lacking energy to do basic things, lack of interest in doing things previously enjoyed b. Specific psychological symptoms: i. Anhedonia: inability to experience pleasure in anything ii. Difficulty concentrating, remembering, making decisions iii. Thoughts of suicide c. Specific physical symptoms: i. Loss of appetite ii. Insomnia/fatigue iii. Crying iv. Diminished sex drive v. Motor retardation or agititation 3. Subtypes of Major Depression: a. Reactive depression: depression in response to a life circumstance b. Endogenous depression: no obvious cause c. Postpartum: associated with childbirth d. Dysthymic disorder: milder form of depression lasting >2 years e. Seasonal Affective disorder: depression symptoms occurring at a particular part of the year f. Psychotic: involves depression with a break from reality 4. Risk Factors for Depression: Stress a. Depressed patients often have increased levels of stress hormones including cortisol, which plays a role in preparing a person to have energy to respond to stress C. Bipolar disorder: cyclical mood swings from depression to mania 1. Characteristics of Bipolar Disorder a. Rates of bipolar disorder are the same in women and men b. Age of onset: typically 20-30 years c. Episodes tend to recur throughout the lifespan d. Two types of bipolar disorder: i. Bipolar I: at least one episode of mania; usually also alternating with depressive episodes ii. Bipolar II: hypomania alternating with depressive episodes iii. Related: Cyclothymic disorder: milder form of bipolar disorder, with patients alternating between hypomania and milder depression 2. Symptoms of Mania a. Psychological: i. Feelings of elation, faultlessness, full of fun, bursting with energy ii. Grandiose thinking iii. Racing thoughts and ideas b. Physical: i. Significantly reduced need for sleep ii. Extremely talkative, impulsive decisions iii. High-risk behavior c. Common comorbid conditions: i. Anxiety disorders ii. Addiction or substance abuse VII. Antidepressants/Mood stabilizers A. The monoamine hypothesis proposed that depression is caused by a reduction in monoamine levels in the CNS and that mania was caused by and increase in monoamines 1. It is still not understood: a. Which of the monoamines is most closely involved in depression b. How the monoamines are related to the symptoms of depression c. Why the neurochemical effects of antidepressants can happen quickly but the therapeutic effects take weeks to happen 2. The noradrenergic and serotonergic neurons in the brainstem can influence one another a. One part of the brainstem sends norepinephrine to the brain and another sends serotonin to the brain b. There are neurons that let these two areas communicate with one another 3. Low levels of serotonin metabolites are found in the brains of people with depression and of people who committed suicide a. Low levels of serotonin do not lead to depression in all people b. Only having low levels of serotonin in the brain is not sufficient to cause depression symptoms B. Four main groups of pharmacological antidepressants 1. Monoamine oxidase inhibitors a. Inhibits monoamine oxidase, an enzyme that metabolizes monoamines in the axon terminal that are NOT packaged into vesicles b. There is more monoamine neurotransmitter to be put into vesicles and released c. Affects dopamine, norepinephrine and serotonin neurons d. Can take several weeks to reach a therapeutic effect e. Have side effects, some of which can be dangerous 2. Tricyclic antidepressants a. Bind to presynaptic neurotransporter proteins, which inhibits reuptake of neurotransmitters into the presynaptic neuron b. Neurotransmitters stay in the synaptic cleft longer and have more effect on the postsynaptic receptors c. Require several weeks to take effect d. Have a small margin of safety: can be fatal at 10x the therapeutic dose 3. Second generation a. Developed for fewer side effects and to be more selective than MAOIs or TCAs b. Have a larger therapeutic index c. Not more effective than MAOIs or TCAs and do not reduce depression symptoms faster d. Two different types: i. Selective monoamine reuptake inhibitors a) SSRIs block the presynaptic reuptake transporter for serotonin b) Side effects are anxiety and sexual dysfunction ii. Atypical antidepressants 4. Third generation: still under development and study C. Mood stabilizers 1. Used to reduce manic and depression symptoms in bipolar disorder a. Not clear why they work 2. Treatment is often life-long because bipolar disorder is highly recurrent 3. Lithium a. Can dramatically reduce mania b. Not as good at treating depression in bipolar disorder, so often used together with an antidepressant c. Very low therapeutic index and blood levels must be monitored frequently to prevent reaching toxic levels VIII. Schizophrenia A. Schizophrenia is a psychiatric disorder characterized by psychotic symptoms 1. Usually a chronic condition 2. Symptoms usually begin in the late teenage years or early 20s 3. Effects men and women in equal numbers B. Symptoms of schizophrenia 1. Psychotic a. Hallucinations: perceiving something is happening that isn’t. i. Often auditory b. Delusions: beliefs not based on reality 2. Nonpsychotic a. Confused communication: illogical, vague, shifts from one subject to an unrelated one b. Emotions that are inappropriate or simply lacking c. Cognitive deficits C. 3 Categories of Symptoms 1. Positive symptoms a. Delusions, hallucinations, disorganized speech b. Patients who mainly have positive symptoms typically started having symptoms later in life and respond well to conventional antipsychotic medications that block D receptors 2 2. Negative symptoms: involve a decline in normal function a. Reduced speech, flattened affect, social withdrawal 3. Cognitive symptoms a. Impaired working memory b. Impaired executive functioning 4. Negative and cognitive symptoms are often resistant to antipsychotic drugs and tend to have an earlier onset of the disease D. Potential Causes of Schizophrenia 1. Abnormalities in brain structure a. Brain imaging studies of schizophrenic patients show: i. Less brain tissue in the basal ganglia and hippocampus ii. Enlarged ventricles b. Schizophrenia is associated with excessive loss of synapses in some brain areas and failure to lose enough synapses in others (brain development) 2. Neuronal organization a. In the hippocampus, neurons are usually arranged in highly organized rows and groups and pointing in the same general direction b. In schizophrenic patients, neurons are disorganized and dendrites don’t reach as far 3. Brain function a. In schizophrenic patients, neurons in the prefrontal cortex do not show as much activity b. Having less neuronal activity in the prefrontal cortex is called hypofrontality and may underlie the negative and cognitive symptoms 4. The dopamine imbalance hypothesis a. Suggests symptoms are due to: i. Reduced dopamine function in mesocortical (VTA -> prefrontal cortex) dopaminergic neurons a) May explain negative symptoms and impaired thinking because neuronal activity in the prefrontal cortex would be reduced ii. Increased dopamine function in mesolimbic (VTA -> HC, amyg, NAc) dopaminergic neurons a) May be responsible for the positive symptoms b. Dopamine receptors D and1D are 2 metabotropic and have opposite effects on neurons 5. Neurodevelopmental model a. Negative symptoms are due to failure of mesocortical pathways early in life, which results in insufficient dopamine in the prefrontal cortex b. Cognitive deficits result because the prefrontal cortex doesn’t function properly c. If the prefrontal cortex isn’t working, it stops controlling mesolimbic dopaminergic neurons d. Too much dopamine in limbic regions causes hallucinations, perceptual distortions, and irrational fears E. The involvement of glutamate in schizophrenia symptoms 1. Inadequate levels of glutamate in the prefrontal cortex can explain a. A decrease in dopamine in the prefrontal cortex i. Glutamatergic neurons go from the prefrontal cortex to the VTA ii. Some of those neurons activate NMDA glutamate receptors on mesocortical cells in the VTA iii. The mesocortical VTA cells then project back to the PFC iv. So if there is not enough glutamate from PFC to VTA, there wont be enough dopamine from VTA to PFC v. This causes deficits in working memory and negative symptoms b. An increase in dopamine in the limbic system i. Other glutamatergic neurons that go from PFC to the VTA excite midbrain GABAergic cells that inhibit mesolimbic dopamine neurons ii. So low activity in PFC glutamatergic neurons fails to inhibit mesolimbic neurons, which means the limbic system gets overexcited iii. This results in positive symptoms IX. Antipsychotics A. The law of thirds 1. One third of patients treated with antipsychotics will have significant symptom reduction as a result of the drugs 2. Another third show improvements in symptoms but may have relapses 3. The other third do not respond well to antipsychotic drugs and will be hospitalized more B. Drugs used to treat schizophrenia 1. Traditional neuroleptics a. Typically effective in reducing positive symptoms but not the negative or cognitive b. Many have significant side effects relating to problems in movement 2. Second generation (atypical) antipsychotics a. Reduce positive symptoms of schizophrenia but don’t have the movement related side effects 3. Neither are consistently more effective than the others C. Effects of Antipsychotic Drugs 1. Most antipsychotic drugs are less successful in treating the negative and cognitive symptoms of schizophrenia 2. Typically prescribed as maintenance therapy to prevent relapse D. Pharmacokinetics of Antipsychotics 1. Antipsychotics can modify multiple neurotransmitter systems but their clinical effectiveness is correlated with their ability to reduce dopamine signaling. a. Blocking dopamine receptors b. Inhibiting dopamine release 2. Older and 2 ndgeneration antipsychotics block D 2 receptors (and other neurotransmitter receptors) a. D 2opamine receptors are inhibitory 3. The D a2toreceptor reduces the amount of dopamine produced. There are two locations: a. Presynaptic D 2utoreceptors i. Because these receptors are on the same cell that is releasing the dopamine that activates them, they are known as autoreceptors ii. When dopamine binds to D 2 autoreceptors on a presynaptic dopamine neuron, it decreases the excitability of the neuron and decreases its release of dopamine b. Postsynaptic D receptors 2 i. Reduce excitability of the neuron E. Pharmacodynamics 1. There is rarely a tolerance for antipsychotic effects (but there can be a tolerance for some side effects such as sedation) 2. Rarely physical dependence or abuse potential 3. Antipsychotics have a very high therapeutic index, so do not typically cause overdose. F. Side Effects of Antipsychotics 1. Parkinsonism a. Movement disorders that resemble symptoms of Parkinson’s disease b. Tremors, slowing or loss of voluntary movement, muscle rigidity, discomfort in legs/inability to sit still c. Due to blockade of dopamine receptors in the basal ganglia 2. Tardive dyskinesia a. A movement disorder that is associated with prolonged use of antipsychotic drugs b. Causes repeated involuntary movements, especially in the face and jaw, but can also be in the limbs c. These movements can be permanent 3. Neuroendocrine effects a. Blocking dopamine receptors can alter function of the neuroendocrine system G. How might antipsychotic drugs be improved? 1. Selective D 2opamine receptor antagonists a. Bind mostly to D r2ceptors b. Effects on the autonomic nervous system are minimal c. Sedation is mild 2. Dopamine system stabilizers a. Abilify is a partial agonist of dopamine receptors, which means it binds readily to dopamine receptors, but doesn’t cause as much of an effect as dopamine itself would b. This reduces positive symptoms c. Abilify can also activate dopamine receptors in areas of the brain where there is too little dopamine, which may reduce the negative symptoms d. Very few side effects 3. Broad-spectrum antipsychotics a. Block multiple types of receptors, in addition to the D receptors 2 b. Clozapine is not more effective than other antipsychotics but its useful in some treatment-resistant patients c. Can reduce negative and cognitive symptoms of schizophrenia d. Causes fewer motor side effects e. Has many other serious side effects so its rarely used X. Parkinson’s Disease A. Consistent characteristics of neurodegenerative diseases: 1. Chronic: lasts a long time and can be controlled but not cured 2. Progressive: symptoms get worse over time 3. Symptoms are not reversible B. Symptoms of Parkinson’s 1. Parkinson’s Disease is a degenerative disease that causes problems with making movements. There is also eventually loss of cognitive function 2. Movement-related symptoms: a. Resting tremor: occurs when limbs are relaxed and disappears when movement is made b. Difficulty in starting movements c. Movements that are made are slow d. Shuffling feet when walking and taking small steps 3. There are also cognitive symptoms 4. Progression of Parkinson’s symptoms a. First symptom can be loss of smell, which occurs because the earliest neuron damage occurs in a region of the brain that processes smell b. Neuron damage then spreads gradually to other parts of the brain 5. Pathophysiology of Parkinson’s (What causes symptoms?) a. Dopamine neurons in the midbrain die and thus no longer supply dopamine to the basal ganglia b. The main culprit is dopamine neurons in the substantia nigra C. Treatment Strategies for Parkinson’s 1. Treatment goal: increase dopamine available a. L-DOPA i. Dopamine itself can’t cross the BBB so it can’t be administered, but L-DOPA can be transported across the BBB and then converted into dopamine ii. This increases the amount of dopamine available b. MAOIs c. Dopamine receptor agonists 2. Surgical Interventions a. It’s possible to remove specific parts of the basal ganglia in such a way that the loss of dopamine can be overcome b. Deep brain stimulation: stimulates regions of the basal ganglia to improve symptoms XI. Alzheimer’s Disease A. Symptoms that develop as Mild Cognitive Impairment progresses to Alzheimer’s 1. General forgetfulness, then progressive loss in memory function 2. Impairment in naming familiar objects or people 3. Misplacing or not finding items B. Pathological changes associated with Alzheimer’s 1. Amyloid Plaques a. A-beta is a normal protein in the brain, but in AD, this protein accumulates to form clumps called “plaques”, which are located between neurons b. Causes degeneration/death of neurons 2. Neurofibrillary tangles (NFTs) a. In AD, tau proteins are altered in a way that they form neurofibrillary tangles inside the neurons b. Causes degeneration/death of neurons C. Diagnosis of AD: brain imaging 1. Since AD is defined by the presence of amyloid plaques and NFTs, there is no definitive test that can confirm a diagnosis prior to post-mortem analysis of the brain tissue 2. Brain imaging techniques can be used to see plaques, but plaques can be present without AD D. Acetylcholine neurons in AD 1. In addition to plaques and tangles, AD is characterized by loss of cholinergic neurons 2. Acetylcholine is an important neurotransmitter in the cortex and hippocampus 3. Ach is involved in learning and memory E. Symptomatic treatments: cholinesterase inhibitors 1. A main neuron type that malfunctions in AD involves neurons that release acetylcholine 2. Acetylcholine is broken down in the synaptic cleft by the enzyme acetylcholinesterase 3. Cholinesterase inhibitors decrease the breakdown of acetylcholine 4. Cannot reverse symptoms or prevent the neuronal damage that causes them XII. Huntington’s Disease A. HD is a neurodegenerative disease that affects movement and cognitive function 1. Unlike other nervous system diseases, there is a clear genetic cause: a trinucleotide repeat B. Symptoms of HD 1. Movement-related: a. Inability to suppress unwanted movement b. Movements are jerky or writhing 2. Cognitive functions a. Thoughts and behaviors are repeated over and over C. Only symptomatic treatments are available for HD. No treatments slow or stop the disease
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