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PSYC 450 Drugs and Behaviour – final exam Study practice Questions and answers complete exam solution Athabasca University
PSYC 450 Drugs and Behaviour – final exam Study practice Questions and answers complete exam solution Athabasca University Define "psychopharmacology." - CORRECT ANSWER The study of drug effects on psychological states and symptoms. Emphasizes drug-induced changes in mood, thinking and behaviour. What is meant by the term "pharmacokinetics"? - CORRECT ANSWER Pharmacokinetics is the process by which drugs are absorbed, distributed within the body, metabolized, and excreted. Bioavailability, which is a measure of the extent of drug absorption for a given drug and route (from 0% to 100%) is related to pharmacokinetics. The factors which contribute to bioavailability constitute the pharmacokinetic component of drug action:
- Routes of administration: how and where the drug is administrated determines how quickly and completely it is absorbed into the blood.
- Absorption and distribution: a drug rarely acts where it initially contacts the body, and so it must pass through a variety of cell membranes and enter the blood plasma, which transports the drug to virtually all of the cells in the body.
- Binding: once in the blood plasma, some drug molecules move to tissues to bind to active target sites (receptors). While in the blood, a drug may also bind (depot binding) to plasma proteins or may be stored temporarily in bone or fat, where it is inactive.
- Inactivation: drug inactivation or biotransformation, occurs primarily as a result of metabolic processes in the liver. The amount of drug in a system depends on the relationship between absorption and inactivation.
- Excretion: the liver metabolites are eliminated from the body with the urine or feces. Some drugs are excreted in an unaltered form by the kidneys. Describe the advantages and disadvantages of intravenous injection. - CORRECT ANSWER Advantages:
- The most rapid and accurate form of drug administration. Disadvantages:
- The quick onset of drug effect with IV injection is potentially hazardous.
- An overdose or allergy leaves little time for corrective measures.
- Produces a more intense subjective drug experience since the drug reaches the brain almost instantly.
- When used with street drugs, impure drugs can lead to toxic reactions and equipment that isn't sterile can cause infections. What are lipid-soluble drugs? - CORRECT ANSWER Drugs with high lipid solubility move through cell membranes by passive diffusion, leaving the water in the blood or stomach juices and entering the lipid layers of membranes. Movement across the membranes is always in a direction from higher to lower concentration. The larger the concentration difference on each side of the membrane (called the concentration gradient), the more rapid the diffusion. Lipid solubility increases the absorption of the drug into the blood and determines how readily a drug will pass the lipid barriers to enter the brain. For example, the narcotic drug heroin is a simple modification of the parent compound morphine. Heroin is more soluble in lipid than morphine, and it penetrates into brain tissue more readily, this having a quicker onset of action and more potent reinforcing properties. This occurs despite the fact that before the psychotropic drug effects occur, the heroin must be converted to morphine by esterase enzymes in the brain. That property makes heroin a prodrug, that is, one that is dependent, on metabolism to convert an active drug to an active one, a process called bioactivation. This strategy is one used by pharmaceutical companies that develop prodrugs that cross the blood- brain barrier if the active drug cannot penetrate easily. Explain the importance of the blood-brain barrier. - CORRECT ANSWER 1. Protects the brain from "foreign substances" in the blood that may injure the brain.
- Protects the brain from neurotransmitters in the rest of the body.
- Maintains a constant environment for the brain. Define "half-life." - CORRECT ANSWER The time required for the amount of drug in the body to decrease by 50%. For example, if the half-life is one day, in 1 day, 50% is left; in 2 days, 25% is left; in 3 days, 12.5% is left; etc.
What is meant by the term "pharmacodynamics"? - CORRECT ANSWER The study of the biochemical and physiologic effects of drugs on the function of living organisms and their component parts (how it works in the body). What are receptors? What are ligands? - CORRECT ANSWER Receptor: any functional macromolecule in a cell to which a drug binds to produce its effects. Ligands: any molecule that binds to a receptor with some selectivity. Describe how receptors can be modified. In other words, explain the life-cycle of receptors. - CORRECT ANSWER There are two principal types of receptors:
- Most drugs and neurotransmitters remain outside the cell and bind to receptors on the exterior cell surface. When these receptors are activated, they initiate changes in an effector, causing intracellular changes such as the movement of ions or changes in enzyme activity. Many hormones are capable of entering the cell before acting on an intracellular receptor that changes the expression of specific genes within the nucleus. The altered protein synthesis in turn leads to changes in cell function that may include altering gluconeogenesis, modulation of the menstrual cycle and others.
- The second type of receptor is found within the target cell, either in the cytoplasm or in the nucleus. Most of the hormones that act on the brain to influence neural events use this type of receptor. Hormonal binding to intracellular receptors alters cell function by triggering changes in the expression of genetic material within the nucleus, producing changes in protein synthesis. Sex hormones act in this way to facilitate mating behaviour and other activities related to reproduction, such as lactation. Differentiate between tolerance and sensitization. - CORRECT ANSWER Tolerance: refers to the decreased effectiveness of a given drug with repeated administration. Sensitization: refers to the increased effectiveness with repeated administration.
Differentiate between metabolic tolerance and pharmacodynamic tolerance. - CORRECT ANSWER Metabolic tolerance: occurs when the body metabolizes drugs at an accelerated rate. Unlike pharmacodynamic tolerance, the drug still affects the brain in the same way. However, the body metabolizes and gets rid of, the drug more quickly. Thus, the same drug has a diminished effect. Pharmacodynamic tolerance: a form of drug tolerance in which the chemistry of the brain becomes adjusted to the presence of the drug, which in turn loses its capacity for modifying brain activity. Can be contrasted with metabolic tolerance, in which the body reacts to the continued presence of the drug by metabolizing it at an increased rate. Both forms of tolerance lead to higher doses of the drug being needed to produce the same effects. What is a neuron? - CORRECT ANSWER A nerve cell; the basic building block of the nervous system. Dendrite - CORRECT ANSWER Branchlike parts of a neuron that are specialized to receive information. Soma - CORRECT ANSWER Cell body of a neuron. Axon - CORRECT ANSWER A threadlike extension of a neuron that carries nerve impulses away from the cell body. Synaptic Terminal - CORRECT ANSWER A bulb at the end of an axon in which neurotransmitter molecules are stored and released. Discuss the functions of two types of glial cells. - CORRECT ANSWER 1. Astrocytes: provide structural and metabolic support for neurons and form the blood-brain barrier.
- Oligodendrocytes: type of glial cell in the CNS that wrap axons in a myelin sheath.
- Schwann cells: type of glia in the PNS, supporting cells of the peripheral nervous system responsible for the formation of myelin.
Resting Potential - CORRECT ANSWER The difference in electric charge between the inside and outside of a neuron's cell membrane. The resting membrane potential of a neuron is about -70 mV (mV=millivolt) - this means that the inside of the neuron is 70 mV less than the outside. At rest, there are relatively more sodium ions outside the neuron and more potassium ions inside that neuron. Epilepsy - CORRECT ANSWER A disorder of the central nervous system characterized by loss of consciousness and convulsions. What are the functions of the spinal cord? - CORRECT ANSWER 1. Control body movements and functions. Signals from your brain to other body parts control your movements. They also direct autonomic (involuntary) functions like your breathing rate and heartbeat, as well as bowel and bladder function.
- Report senses to your brain. Signals from other parts of your body help your brain record and process sensations like pressure or pain.
- Manage your reflexes. Your spinal cord controls some reflexes (involuntary movements) without involving your brain. For example, your spinal cord manages your patellar reflex (involuntarily moving your leg when someone taps your shin in a certain spot). What are the distinct regions of the CNS? - CORRECT ANSWER At its most basic level, the CNS consists of the brain and spinal cord. In more detail, the central nervous system is usually considered to have seven basic parts:
- The spinal cord.
- The medulla.
- The pons.
- The cerebellum.
- The midbrain.
- The diencephalon.
- The cerebral hemispheres.
The medulla, pons, and midbrain are collectively called the brainstem; the diencephalon and cerebral hemispheres are collectively called the forebrain. Within the brainstem are found cranial nerve nuclei that either receive input from cranial sensory ganglia via their respective cranial sensory nerves or give rise to axons that constitute cranial motor nerves. In addition, the brainstem is the conduit for several major tracts in the central nervous system. These tracts either relay sensory information from the spinal cord and brainstem to the midbrain and forebrain or relay motor commands from the midbrain and forebrain back to motor neurons in the brainstem and spinal cord. What is the function of the diencephalon? - CORRECT ANSWER The diencephalon acts as a primary relay and processing center for sensory information and autonomic control. The plethora of communicating pathways between these structures and other parts of the body makes the diencephalon a functionally diverse area. List and describe the major parts of the limbic system. - CORRECT ANSWER 1. Hippocampus: plays a vital role in regulating learning, memory encoding, memory consolidation, and spatial navigation.
- Amygdala: emotional responses, including feelings of happiness, fear, anger, and anxiety. This area is also key for the formation of new memories.
- Hypothalamus: responsible for regulating your hunger, thirst, response to pain, levels of pleasure, sexual satisfaction, anger and aggressive behaviour, and more. It also regulates the functioning of the autonomic nervous system which in turn regulates things like pulse, blood pressure, breathing, and arousal in response to emotional circumstances.
- Thalamus: involved in sensory perception and regulation of motor functions (i.e., movement). It connects areas of the cerebral cortex that are involved in sensory perception and movement with other parts of the brain and spinal cord that also have a role in sensation and movement.
- Prefrontal cortex: facilitate a top-down control of the execution of goal-directed behaviours. The PFC sends glutamatergic outputs to limbic areas such as the hippocampus and amygdala which in turn modulate the activity of the nucleus accumbens.
- Pituitary gland: pumps hormones called releasing factors into the bloodstream. As you know, the pituitary is the so-called "master gland," and these hormones are vitally important in regulating growth and metabolism.
- Brain stem: involved in integrated functions such as social interaction, interoception, emotion regulation, spatial discrimination, etc., which might be manifested under interaction between the subcortical and cortical systems
What is a synapse? Give two examples. - CORRECT ANSWER Synapses are part of the circuit that connects sensory organs, like those that detect pain or touch, in the peripheral nervous system to the brain. Synapses connect neurons in the brain to neurons in the rest of the body and from those neurons to the muscles.
- Electrical synapse: is a gap which has channel proteins connecting the two neurons so that the electrical signal can travel straight over the synapse.
- Chemical synapse: is a gap between two neurons where information passes chemically, in the form of neurotransmitter molecules. While electrical synapses are faster (electricity moves quicker than molecules, and you don't need receptors), they lack gain. The electrical signal is always the same or smaller after a synapse, while chemicals can increase a signal. Electrical synapses also have to be much smaller so the channel proteins can reach from one cell to another. You often find electrical synapses in systems requiring quick responses, like instincts and defense, and chemical synapses in the less urgent places. What is a neurotransmitter? What is a classical neurotransmitter? - CORRECT ANSWER Neurotransmitters: often referred to as the body's chemical messengers. They are the molecules used by the nervous system to transmit messages between neurons, or from neurons to muscles. Communication between two neurons happens in the synaptic cleft (the small gap between the synapses of neurons). Here, electrical signals that have travelled along the axon are briefly converted into chemical ones through the release of neurotransmitters, causing a specific response in the receiving neuron. A neurotransmitter influences a neuron in one of three ways: excitatory, inhibitory or modulatory. Classical neurotransmitter: among the small molecules constituting the "classical" neurotransmitters, the best known are:
- Acetylcholine.
- Serotonin.
- Catecholamines, including epinephrine, norepinephrine, and dopamine.
- Excitatory amino acids such as aspartate and glutamate (half of the synapses in the central nervous system are glutamatergic).
- Inhibitory amino acids such as glycine and gamma-aminobutyric acid (GABA; one-quarter to one- third of the synapses in the central nervous system are GABAergic).
- Histamine.
- Adenosine.
- Adenosine triphosphate (ATP). How is the synaptic transmitter action of a released chemical terminated? Give two examples. - CORRECT ANSWER 1. Reuptake: a process in which neurotransmitters are sponged up from the synaptic cleft by the presynaptic membrane.
- Enzymatic degradation in the cleft: a way of removing excess neurotransmitter from the synapse, in which enzymes specific for that neurotransmitter bind with the neurotransmitter and destroy it.
- Diffusion: the process by which molecules move from an area of higher concentration to an area of lower concentration. When a neurotransmitter binds to a receptor on the postsynaptic side of the synapse and changes the postsynaptic cell's excitability. Describe the two major types of receptors. - CORRECT ANSWER Ionotropic: a group of transmembrane ion channels that open or close in response to the binding of a chemical messenger (ligand) such as a neurotransmitter. Metabotropic: a subtype of membrane receptors that do not form an ion channel pore but use signal transduction mechanisms, often G proteins, to activate a series of intracellular events using second messenger chemicals. Why is nitric oxide considered to be an atypical neurotransmitter? - CORRECT ANSWER NO is a short- lived gas not to be confused with the relatively stable anesthetic gas nitrous oxide (laughing gas). NO is actually a free radical and is therefore a highly reactive compound. Some of its toxic effects are likely due to NO reacting with superoxide to produce the destructive radical peroxynitrite. NO is considered an unconventional neurotransmitter because it is not released by exocytosis and its action does not occur through conventional receptor molecules. As mentioned previously, the typical description of neuronal communication considers transmission to be unidirectional. A presynaptic neurotransmitter is released that produces changes in the postsynaptic neuron. Several compounds (like neuropeptides and NO) produced in postsynaptic neurons diffuse into the local environment and affect the surrounding cells. Since NO is a freely diffusible gas it has the potential to travel quickly in any direction from its point of production. For example, if produced in a postsynaptic cell because of glutamate receptor stimulation, NO could be released into the local environment and send a signal back to the presynaptic neuron. Describe four ways in which drugs can alter synaptic transmission. - CORRECT ANSWER 1. Stimulate or inhibit the release of neurotransmitters.
- Mimic the effects of neurotransmitters on postsynaptic receptors.
- Block these effects.
- Interfere with the reuptake of a neurotransmitter once it is released. Describe the importance of the endocrine system. - CORRECT ANSWER Your endocrine system continuously monitors the number of hormones in your blood. Hormones deliver their messages by locking into the cells they target so they can relay the message. The pituitary gland senses when your hormone levels rise and tells other glands to stop producing and releasing hormones. When hormone levels dip below a certain point, the pituitary gland can instruct other glands to produce and release more. This process, called homeostasis, works similarly to the thermostat in your house. Hormones affect nearly every process in your body, including:
- Metabolism (the way you break down food and get energy from nutrients).
- Growth and development.
- Emotions and mood.
- Fertility and sexual function.
- Sleep.
- Blood pressure. Explain the organization of the hypothalamic-pituitary axis. - CORRECT ANSWER The hypothalamic- pituitary-adrenal axis, or HPA axis as it is commonly called, describes the interaction between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus and pituitary gland are located just above the brainstem, while the adrenal glands are found on top of the kidneys. The hypothalamic-pituitary-adrenal axis, or HPA axis, is a term used to represent the interaction between the hypothalamus, pituitary gland, and adrenal glands; it plays an important role in the body's response to stress. The pathway of the axis results in the production of cortisol. The aim of the stress response is to provide energy for a long period of time. It does not need to be fast so it uses hormones as a way of transmitting signals. Discuss the process of stereotaxic surgery. - CORRECT ANSWER Stereotactic surgery is a minimally invasive form of surgical intervention that makes use of a three-dimensional coordinate system to locate small targets inside the body and to perform on them some action such as ablation, biopsy, lesion, injection, stimulation, implantation, radiosurgery (SRS), etc.
What is microdialysis? - CORRECT ANSWER A procedure for analyzing chemicals present in the interstitial fluid through a small piece of tubing made of a semipermeable membrane that is implanted in the brain. What is in situ hybridization? - CORRECT ANSWER A laboratory technique used to localize a sequence of DNA or RNA in a biological sample. In this technique, a biological sample consisting of tissue sections, cells or chromosomes from an individual is affixed to a glass slide and then exposed to a "probe"—a small piece of single-stranded DNA tagged with a chemical or fluorescent dye. The labelled probe finds and then binds to its matching sequence within the biological sample. The location of the bound probe can then be seen with the use of a microscope. Differentiate between PET and MRI. - CORRECT ANSWER PET: a visual display of brain activity that detects where a radioactive form of glucose goes while the brain performs a given task. MRI: a technique that uses magnetic fields and radio waves to produce computer-generated images that distinguish among different types of soft tissue; allows us to see structures within the brain. Explain the utility of using knockout technology. - CORRECT ANSWER Knocking out a gene means to mutate the DNA in a way that stops the gene's expression permanently. This is possible in all kinds of cells and organisms, using specific genetic approaches. Currently, the fastest and most direct approach to achieving specific gene knockout is to use CRISPR genome editing. Outline the process of drug development and testing. - CORRECT ANSWER 1. Discovery and development: research for a new drug begins in the laboratory.
- Preclinical research: drugs undergo laboratory and animal testing to answer basic questions about safety.
- Clinical research: drugs are tested on people to make sure they are safe and effective.
- FDA review: FDA review teams thoroughly examine all of the submitted data related to the drug or device and make a decision to approve or not to approve it.
- FDA post-market safety monitoring: FDA monitors all drug and device safety once products are available for use by the public.
What is operant conditioning? Give an example of its use. - CORRECT ANSWER The learning of voluntary behaviour through the effects of pleasant and unpleasant consequences to responses. E.g. an animal rewarded for performing a certain behaviour. Name three catecholamine neurotransmitters. How are they synthesized? - CORRECT ANSWER 1. Dopamine: is synthesized in the nerve terminal from tyrosine which is transported across the blood- brain barrier. We include an exchange between tyrosine and a tyrosine pool that represents all the other uses and sources of tyrosine in the terminal.
- Epinephrine: synthesized via methylation of the primary distal amine of norepinephrine by phenylethanolamine N-methyltransferase (PNMT) in the cytosol of adrenergic neurons and cells of the adrenal medulla (so-called chromaffin cells).
- Norepinephrine: synthesized from dopamine by dopamine β-hydroxylase. [7] It is released from the adrenal medulla into the blood as a hormone and is also a neurotransmitter in the central nervous system and sympathetic nervous system where it is released from noradrenergic neurons. How are catecholamines inactivated? - CORRECT ANSWER Catabolic processes are just as important for the proper functioning of cells and organisms as are anabolic processes. This is no less true for neurotransmitters such as catecholamines. The catecholamines epinephrine, norepinephrine, and dopamine are inactivated by oxidation reactions catalyzed by monoamine oxidase (MAO) (Figure 1). Catecholamines must be transported out of the synaptic cleft before inactivation because MAO is located in nerve endings. (The process by which neurotransmitters are transported back into nerve cells so that they can be reused or degraded is referred to as reuptake.) Epinephrine, released as a hormone from the adrenal gland, is carried in the blood and is catabolized in non-neural tissue (perhaps the kidney). Catecholamines are also inactivated in methylation reactions catalyzed by catechol-O-methyltransferase (COMT). These two enzymes (MAO and COMT) work together to produce a large variety of oxidized and methylated metabolites of the catecholamines. Describe two important dopaminergic pathways. - CORRECT ANSWER 1. Mesocortical: runs from the ventral tegmental area to the cerebral cortex. It forms extensive connections with the frontal lobes and is thought to be important to a wide range of functions, such as motivation, emotion, and executive functions.
- Mesolimbic: consists of dopaminergic neurons that originate in the ventral tegmental area (VTA) of the brain and project to the nucleus accumbens, amygdala, and hippocampus.
- Nigrostriatal: a bilateral dopaminergic pathway in the brain that connects the substantia nigra pars compacta (SNc) in the midbrain with the dorsal striatum (i.e., the caudate nucleus and putamen) in the forebrain.
- Tuberoinfundibular: one of the major dopamine pathways in the brain originating from hypothalamus. The release of dopamine in this pathway regulates prolactin secretion by the pituitary gland. What is Parkinson's disease? - CORRECT ANSWER A progressive disease that destroys brain cells and is identified by muscular tremors, slowing of movement, and partial facial paralysis. Parkinson's disease is caused by a loss of nerve cells in the part of the brain called the substantia nigra. Nerve cells in this part of the brain are responsible for producing a chemical called dopamine. Differentiate the two major families of dopamine receptors. - CORRECT ANSWER The five dopamine receptor subtypes (D1- D5) can be classified into two major families of receptors. The D1 receptor family has a long C-terminal tail and a short cytoplasmic loop between transmembrane helices 5 and 6, whereas the D2 receptor family has a short C-terminal tail and a long cytoplasmic loop between helices 5 and 6. Stimulation of the D1 family is excitatory, increasing cAMP and intracellular Ca2+ levels and activating protein kinase C (PKC). Stimulation of the D2 family is inhibitory, decreasing cAMP and intracellular Ca2+ levels and hyperpolarizing the cell. The five receptor subtypes exhibit distinctive patterns of distribution in the central nervous system. Within the D2 receptor subtype, there are D2S and D2L isoforms (not shown).IP3, inositol trisphosphate; PIP2, phosphatidylinositol-4,5-bisphosphate
Describe the ascending noradrenergic pathway. - CORRECT ANSWER The central noradrenergic system is composed of two primary ascending projections that originate from the brainstem: The dorsal noradrenergic bundle (DNB), and the ventral noradrenergic bundle (VNB). The DNB originates from the A6 locus coeruleus, located in the dorsal pons, and is composed of primarily noradrenergic neurons. It functions as the predominant site of norepinephrine production in the central nervous system. It sends projections to innervate the cerebral cortex, hippocampus, and cerebellum exclusively and has projections that overlap with projections from the VNB to innervate areas of the amygdala, hypothalamus, and spinal cord. The VNB originates from nuclei in the pons and medulla and sends projections to innervate the amygdala, hypothalamus, and areas of the midbrain and medulla. What do adrenergic agonists do? - CORRECT ANSWER Adrenergic agonists are drugs that work by mimicking the functioning of the sympathetic nervous system—the part of the nervous system that increases heart rate, blood pressure, breathing rate, and eye pupil size. How are adrenergic drugs useful in treating medical conditions? - CORRECT ANSWER Adrenergic drugs stimulate the nerves in your body's sympathetic nervous system (SNS). This system helps regulate your body's reaction to stress or emergency. Describe how serotonin is synthesized and inactivated. - CORRECT ANSWER Serotonin is synthesized in serotonergic terminals from tryptophan, which competes with tyrosine and the branched-chain amino acids for transport across the blood-brain barrier. L-tryptophan is converted to 5- hydroxytryptophan, which is then turned into 5-hydroxytryptamine (serotonin or 5-HT). Secreted serotonin is inactivated in the synaptic cleft by reuptake via a serotonin-specific transporter (SERT). Discuss the anatomy of the serotonergic pathways. - CORRECT ANSWER Serotonin neurons are primarily found in the brainstem in clusters of neurons called the raphe nuclei.
Serotonin neurons from the raphe nuclei project throughout the brainstem and brain and provide serotonin to the rest of the CNS. There are 7 serotonin receptor families:
- 6 are g-protein-coupled receptors.
- 1 is a ligand-gated ion channel.
- There are 14 different receptor subtypes. Serotonin is removed from the synaptic cleft via reuptake by the serotonin transporter (SERT). Serotonin is linked to mood. How is serotonin associated with obesity? - CORRECT ANSWER Plays a role in appetite regulation. Serotonin is a neurotransmitter, that, when released, brings about feelings of calm, happiness, peace, and satisfaction. Redux and fenfluramine-enhanced circulation of serotonin in the brain creates greater and longer feelings of fullness. Also, too much peripheral serotonin in the blood inhibits the brown fat that burns energy and glucose to make heat, which leads to obesity and the development of diabetes. Describe the two main serotonergic receptor subtypes. - CORRECT ANSWER 5-HT1A:
- Located in the presynaptic and postsynaptic regions.
- Activation of this receptor has been involved in the mechanism of action of anxiolytic, antidepressant and antipsychotic medications.
- G-protein coupled receptors that exert their effects through Gi/o proteins to inhibit adenylyl cyclase, as well as other second messenger cascades such as MAPK pathways and NMDA receptor channels.
- Postsynaptic 5-HT1A receptors are found in those regions of the brain that are implicated in the control of mood, cognition and memory.
5-HT2A:
- G protein-coupled receptor.
- A cell surface receptor, but has several intracellular locations.
- Generally concentrated in the frontal cortex.
- Activation of these receptors in the central nervous system results in an increase in body temperature. How is acetylcholine synthesized? How is it inactivated? - CORRECT ANSWER Acetylcholine is synthesized in nerve terminals from acetyl coenzyme A (acetyl CoA, which is synthesized from glucose) and choline, in a reaction catalyzed by choline acetyltransferase (CAT) (Figure 6.8). The presence of CAT in a neuron is thus a strong indication that ACh is used as one of its transmitters. The action of acetylcholine in the synapse is terminated by an enzyme called acetylcholinesterase which breaks down acetylcholine into acetate and choline. The choline is then transported back into neurons to synthesize more acetylcholine. Describe the anatomy of the cholinergic pathways. - CORRECT ANSWER There are several clusters of cholinergic neurons throughout the brain. Acetylcholine is used at neuromuscular junctions to cause muscle contraction, in the ANS (in all preganglionic neurons and postganglionic parasympathetic neurons) and plays an important role in memory, arousal and attention. Some are found in the basal forebrain and include the:
- Medial septal nucleus.
- Nucleus of the diagonal band.
- Nucleus basalis. Others are found in the brainstem, including the pedunculopontine nucleus and laterodorsally tegmental nucleus.
Acetylcholine acts on two families of receptors, and each receptor family has several subtypes. Describe the cholinergic receptor subtypes. - CORRECT ANSWER Ionotropic: they are called nicotinic acetylcholine receptors because nicotine also binds to and activates the receptors. Their activation generally results in the excitation of the neuron. Metabotropic: these are called muscarinic acetylcholine receptors because a substance called muscarine binds to them. Their effects depend on the subtype of the receptor. What is Alzheimer's disease? - CORRECT ANSWER A progressive and irreversible brain disorder characterized by gradual deterioration of memory, reasoning, language, and, finally, physical functioning. The causes probably include a combination of age-related changes in the brain, along with genetic, environmental, and lifestyle factors. The importance of any one of these factors in increasing or decreasing the risk of Alzheimer's disease may differ from person to person. What is glutamate? How is it synthesized? - CORRECT ANSWER Glutamate is a major excitatory neurotransmitter that is involved in memory. Nearly all excitatory neurons in the CNS are glutamatergic. As an amino acid that cannot cross the blood-brain barrier, glutamate has to be synthesized in neurons via local precursors. Glutamine is the most prevalent precursor. Glutamate synthesis:
- Glial cells release glutamine.
- Glutamine reaches the presynaptic terminals.
- Glutaminase (a mitochondrial enzyme) metabolizes glutamine.
- The glutamine becomes glutamate. Describe what ionotropic glutamate receptors are. - CORRECT ANSWER Ionotropic glutamate receptors consist of AMPA, Kainate, and NMDA. Ionotropic glutamate receptors depolarize the membrane of the postsynaptic cell, which leads to an excitatory response. iGluRs mediate fast excitatory neurotransmission and are involved in synaptic plasticity and our capacity to learn and form memories. As nonselective cation channels, iGluRs allow ions like Na+, K+ or Ca2+ to pass through the channel upon binding with glutamate1,4. Activation of a significant number of iGluRs generates an action potential (AP). After this signal is received, excitatory amino acid transporters (EAATs) remove glutamate from the synaptic cleft, effectively turning off the signal in preparation for subsequent APs. Describe the functions of metabotropic glutamate receptors. - CORRECT ANSWER These G-protein coupled receptors indirectly activate secondary messengers that influence the passage of ions in and out of the neuron. Metabotropic glutamate receptors are widely distributed though out the brain, and they participate in many normal functions, including locomotor activity, motor coordination, cognition, mood, and pain perception. The metabotropic glutamate receptors (mGluRs) are family C G-protein-coupled receptors that mediate synaptic transmission and neuronal excitability throughout the central nervous system. The mGluRs bind glutamate within a large extracellular domain and transmit signals through the receptor protein to intracellular signalling partners. Discuss the role of glutamate receptors in long-term potentiation. - CORRECT ANSWER Long-term potentiation is a gradual strengthening of the connections among neurons from repetitive stimulation.
NMDA glutamate receptors, in particular, are a necessary component in memory formation, as modeled by long term potentiation. The most direct evidence for this is that, when drugs that block NMDA receptors are administered to rats, long term potentiation does not occur. The mechanism by which NMDA has its effects, appears to be via calcium (Ca2 +) ion channels. Research indicates that Ca2 + channels, which are normally blocked by magnesium (Mg2 +), open when glutamate activates NMDA receptors, with one important qualifier. The membrane must already be partly depolarized - an EPSP must be in progress. Research indicates that, even if Ca2 + channels are activated, long term potentiation will not occur, if the post synaptic membrane is not partly depolarized. This explains why, in long term potentiation, many pulses in quick succession are necessary. Thus, two important criteria must be met for long term potentiation to occur. NMDA receptors must be activated, and the membrane of the post synaptic neuron must be partially depolarized. The Ca2 + channels are, therefore, neurotransmitter and voltage dependent. What is GABA? How is it inactivated? - CORRECT ANSWER GABA is a major inhibitory amino acid neurotransmitter in the brain. GABA breakdown occurs through a combination of neuronal, and astroglial uptake, and a cellular mechanism for metabolizing and recycling this neurotransmitter.
- Starts with the enzyme GABA aminotransferase (GABA-T).
- GABA-T is present in both GABAergic neurons and astrocytes.
- Through these pathways, GABA-T is eventually turned into succinate.
- One molecule of glutamate is formed for every molecule of GABA that is broken down. Describe the structure and function of the GABAA receptor. - CORRECT ANSWER GABAA receptors are responsible for most fast inhibitory synaptic transmission in the vertebrate CNS. Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, insomnia and anxiety. GABAA receptors are ionotropic. GABAA receptors are ion channels that allow chloride ions to move across the cell membrane from outside to inside. This process inhibits the postsynaptic cell as a result of membrane hyperpolarization.
Structure:
- GABAA receptors are multiunit proteins. Each receptor contains 5 subunits.
- 3 or 4 different kinds of subunits may be found within a particular GABAA receptor complex.
- Most GABAA receptors are thought to contain two alpha subunits, two beta subunits, and one y subunit. A small number of receptors contain a g subunit instead of a y subunit. Describe the structure and function of the GABAB receptor. - CORRECT ANSWER GABAB receptors are metabotropic.
- Requires two different subunits in order to assemble in the membrane and work properly.
- Exerts an inhibitory effect on the postsynaptic cell.
- The inhibitory effect is mediated by a few mechanisms, including inhibition of cAMP formation, and stimulation of K^+ channel opening.
- Drugs that function as agonists or antagonists at GABAA receptors have no effect on the GABAB receptor. However, it can be activated by an agonist called baclofen, which is used as a muscle relaxant and an antispastic agent. What are anxiolytics drugs? How do they work? - CORRECT ANSWER Anxiolytics are used to treat anxiety symptoms or disorders. They're sometimes called anti-anxiety medications or minor tranquillizers. Anxiolytic medications are habit-forming and can lead to dependency or a substance use disorder. Anxiolytics target specific chemical messengers in the brain (serotonin, dopamine, and GABA). A common class of anxiolytics includes benzodiazepines, which extend the life of GABA within the synapses. These drugs are habit-forming, and so dependence can be a problem. Individuals can also build a tolerance for them. Define "drug addiction." What is substance dependence? - CORRECT ANSWER Addiction is an inability to stop taking a drug despite adverse consequences, whereas dependence is typically physical reliance on a drug characterized by withdrawal symptoms.
Drug addiction: loss of control over drug intake or compulsive seeking and taking of drugs, despite adverse consequences. Substance dependence: a maladaptive pattern of substance use is characterized by the need for increased amounts to achieve the desired effect, negative physical effects when the substance is withdrawn, unsuccessful efforts to control its use and substantial effort expended to seek it or recover from its effects. Also known as addiction. Explain the "gateway" theory of drug use. - CORRECT ANSWER The gateway drug effect (alternatively, stepping-stone theory, escalation hypothesis, or progression hypothesis) is a comprehensive catchphrase for the often observed effect that the use of a psychoactive substance is coupled to an increased probability of the use of further substances. Describe the physical dependence model of addiction. - CORRECT ANSWER Physical-dependence- based theories of addiction regard compulsive drug taking as the behavioural manifestation of a desperate need to relieve aversive autonomic withdrawal symptoms. The repeated use of a specific substance (which could be legal - i.e. alcohol or prescription medication
- or illicit) causes the user's body to adapt to the regular presence of that substance, and to depend upon it for normal functioning. Upon cessation of use (when the user stops taking the substance in question) the user's system may react to the "abnormal" absence of the substance by the manifestation of various (frequently unpleasant) symptoms collectively known as withdrawal. Discuss the limitations of the positive reinforcement model of addiction. - CORRECT ANSWER Positive reinforcement model of addiction: rewarding aspects of the drug reinforce the act of taking/using the drug. Limitations: in the case of addiction/dependence, one could argue that the taking of drugs is actually negative reinforcement. The stimulus is withdrawal symptoms, to which the drug's effects are introduced to remove. So instead of the desirable effects of the drug acting as a positive reinforcer, the drug's effects actually just take away the adverse effects of withdrawal.
Discuss the neural mechanisms of reward. - CORRECT ANSWER Pathway within the limbic system that is associated with feelings of reward in day-to-day life and the feelings of pleasure that lead to craving and addiction. Activation of this pathway by addictive drugs leads to increase levels of dopamine. How is ethanol produced? - CORRECT ANSWER 1. Milling: corn kernels are milled into flour.
- Liquefaction: water is added to make a slurry.
- Saccharification: starch molecules are broken down into glucose.
- Fermentation: yeast is added.
- Distillation and dehydration: this process concentrates and purifies the ethanol.
- Denaturation: gasoline is added to make it undrinkable. Describe the process of alcohol metabolism. - CORRECT ANSWER 1. Broken down, or metabolized, by an enzyme in your liver cells known as alcohol dehydrogenase (ADH).
- ADH breaks down alcohol into acetaldehyde.
- Aldehyde dehydrogenase (ALDH), rapidly breaks down acetaldehyde into acetate. What are DTs? - CORRECT ANSWER Delirium tremens, also called DTs or alcohol withdrawal delirium (AWD), is a severe type of withdrawal from alcohol. It usually starts about 2 to 3 days after someone who's dependent on alcohol ends a long drinking binge. DTs usually lasts for 2 to 3 days, but symptoms may linger for as long as a week. About 5% of people in alcohol withdrawal get DTs. If untreated, delirium tremens can cause a heart attack, stroke, and death. Discuss the neurotoxic effects of heavy alcohol consumption. - CORRECT ANSWER 1. Increase oxidative stress.
- Inflammation.
- Cognitive deficits.
- Can induce Wernicke's disease, Korsakoff's psychosis, epilepsy, cerebellar syndrome, and alcoholic dementia. Certain neurons containing the peptide vasopressin may be sensitive to chronic alcohol-induced neurotoxicity. Additionally, heavy alcohol consumption can cause hypersensitivity in NMDA receptors, resulting in excitotoxicity which can in turn lead to neurodegenerative diseases. Describe the effects of alcohol in other body organ systems. - CORRECT ANSWER Cardiovascular system: heart rate increases. Excretory system: drinker looses more water from body than usual. Digestive system: too much alcohol in the stomach may cause vomiting. Nervous system: brain slows down. Alcohol can harm the brain, liver, heart and digestive system. Drinking during pregnancy can affect the fetus, and cause fetal alcohol syndrome. How does alcohol affect glutamate? - CORRECT ANSWER Normally, glutamate would increase brain activity and energy levels, but alcohol inhibits and suppresses the release of the excitatory neurotransmitter. Discuss the major psychological factors associated with alcoholism. - CORRECT ANSWER 1. High life stress.
- Nonadaptive coping styles.
- Parental and peer substance use.
- Little parental support.
- Low level of academic competence.
- Poor behavioural control. What are the two major pharmacotherapeutic approaches in treating alcoholism? Describe the drugs used in these approaches. - CORRECT ANSWER 1. Making alcohol ingestion unpleasant: disulfiram (Antabuse) makes the ingestion of alcohol extremely unpleasant. However, many people trying the treatment end up quitting.
- Reducing its reinforcing qualities: naltrexone is used to reduce the subjective high feeling of alcohol, reducing rates of abuse. List and briefly describe the five major factors that determine the pharmacokinetics of drug action. - CORRECT ANSWER 1. Routes of administration: some routes are faster/slower than others.
- Absorption and distribution: how the drug is absorbed and distributed in the bloodstream.
- Binding: how effectively the drug binds to receptors once in the brain.
- Inactivation: changing the molecular structure of a drug to be excreted as metabolites.
- Excretion: how long it takes for half the drug to be eliminated. Describe how drugs that block the D2 dopamine receptor alter prolactin levels and release. - CORRECT ANSWER Drugs such as conventional antipsychotics block dopamine D2 receptors in the tuberoinfundibular DA pathway, which causes plasma prolactin concentrations to rise, a condition called hyperprolactinemia. Describe the procedure of microdialysis, list its advantages, and provide an example of how it might be used to study the nervous system. - CORRECT ANSWER Procedure:
- Subject is placed in a stereotaxic frame.
- Semi-permeable membrane-containing probe is inserted in the ventral hippocampus.
- Subject recovers for 24 hours.
- Perfusion fluid is pumped into the probe via a perfusion pump and dialysate is collected after equilibration.
- Analytes are quantified and characterized. Advantages:
- Enables sampling and collection of small molecular-weight substances from the interstitial space.
- Permits quantification of neurotransmitters, peptides and hormones in the behaving animal. One of the only ways to do this. An example of when microdialysis might be used is if one identical twin has schizophrenia. The other has a greater likelihood of getting it, so measuring the 2nd twin's pre-synaptic cell secretions would be s good way to assess this. Describe the HPA axis and the neuroendocrine stress response, including the idea of negative feedback. - CORRECT ANSWER The HPA axis is the interaction between the nervous and endocrine systems to produce the body's response to stress. Elevated levels of one of these hormones may lead to depression. Involves the hypothalamus, pituitary gland, and adrenal cortex. Disruptions in homeostasis (i.e., stress) place demands on the body that are met by the activation of 2 systems, the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). Stressor-induced activation of the HPA axis and the SNS results in a series of neural and endocrine adaptations known as the stress response or stress cascade. The stress cascade is responsible for allowing the body to make the necessary physiological and metabolic changes required to cope with the demands of a homeostatic challenge. Cortisol is often released for several hours after encountering a stressor. At a certain blood concentration of cortisol in the blood stream, this is sensed by receptors in the areas of the brain such as the hypothalamus and hippocampus. The cortisol exerts what is known as negative feedback to the hypothalamus which releases CRH, therefore inhibiting this hormonal release. Cortisol also inhibits the anterior pituitary gland which releases ACTH, thus inhibiting this hormonal release.